A PROCESS AND INTERMEDIATE COMPOUNDS USEFUL FOR THE PREPARATION OF PLATELET GLYCOPROTEIN IIb/IIIa INHIBITORS CONTAINING N< alpha >-METHYLARGININE

Abstract: The present invention provides processes for the preparation of platelet glycoprotein IIb/IIIa inhibitors of formula (I). The present invention also provides processes for the preparation of intermediate compounds. Finally, the invention provides intermediate compounds useful in said processes for the preparation of platelet glycoprotein IIb/IIIa inhibitors.

Description: TTTLF. A Process And Intermediate Compounds Useful For The Preparation Of Platelet Glycoprotein Ilb/IIIa Inhibitors Containing N α -methylarginine FIELD OF THE INVENTION This invention relates to processes for the synthesis of platelet glycoprotein Ilb/IIIa inhibitors, and to intermediate compounds useful in said processes. BACKGROUND OF THE INVENTION Activation of platelets and the resulting platelet aggregation and secretion of factors by the platelets have been associated with different pathophysiological conditions including cardiovascular and cerebrovascular thromboembolic disorders, for example, the thromboembolic disorders associated with unstable angina, myocardial infarction, transient ischemic attack, stroke, atherosclerosis and diabetes. The contribution of platelets to these disease processes stems from their ability to form aggregates, or platelet thrombi, especially in the arterial wall following injury. Platelets are known to play an essential role in the maintenance of hemostasis and in the pathogenesis of arterial thrombosis. Platelet activation has been shown to be enhanced during coronary thrombolysis which can lead to delayed reperfusion and reocclusion. Clinical studies with aspirin, ticlopidine and a monoclonal antibody for platelet glycoprotein Ilb/IIIa provide biochemical evidence for platelet involvement in unstable angina, early stage of acute myocardial infarction, transient ischemic attack, cerebral ischemia, and stroke. Platelets are activated by a wide variety of agonists resulting in platelet shape change, secretion of granular contents and aggregation. Aggregation of . platelets serves to further focus clot formation by concentrating activated clotting factors in one site. Several endogenous agonists including adenosine diphosphate (ADP) , serotonin, arachidonic acid, thrombin, and collagen, have been identified. Because of the involvement of several endogenous agonists in activating platelet function and aggregation, an inhibitor which acts against all agonists would represent a more efficacious antiplatelet agent than currently available antiplatelet drugs, which are agonist-specific. Current antiplatelet drugs are effective against only one type of agonist; these include aspirin, which acts against arachidonic acid; ticlopidine, which acts against ADP; thromboxane A2 synthetase inhibitors or receptor antagonists, which act against thromboxane A2; and hirudin, which acts against thrombin. Recently, a common pathway for all known agonists has been identified, namely platelet glycoprotein Ilb/IIIa complex (GPIIb/IIIa), which is the membrane protein mediating platelet aggregation. A recent review of GPIIb/IIIa is provided by Phillips et al. (1991) Cell 65: 359-362. The development of a GPIIb/IIIa antagonist represents a promising new approach for antiplatelet therapy. Recent studies in man with a monoclonal antibody for GPIIb/IIIa indicate the antithrombotic benefit of a GPIIb/IIIa antagonist. There is presently a need for a GPIIb/IIIa-specific antiplatelet agent which inhibits the activation and aggregation of platelets in response to any agonist. Such an agent should represent a more efficacious antiplatelet therapy than the currently available agonist-specific platelet inhibitors. GPIIb/IIIa does not bind soluble proteins on unstimulated platelets, but GPIIb/IIIa in activated platelets is known to bind four soluble adhesive proteins, namely fibrinogen, von Willebrand factor, fibronectin, and vitronectin. The binding of fibrinogen and von Willebrand factor to GPIIb/IIIa causes platelets to aggregate. The binding of fibrinogen is mediated in part by the Arg-Gly-Asp (RGD) recognition sequence which is common to the adhesive proteins that bind GPIIb/IIIa. Several RGD-containing peptides and related compounds have been reported which block fibrinogen binding and prevent the formation of platelet thrombi. For example, see Cadroy et al. (1989) J. Clin . Invest . 84: 939-944; Klein et al. U.S. Patent 4,952,562, issued 8/28/90; European Patent Application EP 0319506 A; European Patent Application EP 0422938 Al; European Patent Application EP 0422937 Al; European Patent Application EP 0341915 A2; PCT Patent Application WO 89/07609; PCT Patent Application WO 90/02751; PCT Patent Application WO 91/04247; and European Patent Application EP 0343085 Al. Compounds of formula (I) below are difficult to prepare. A key difficulty in the synthesis of this class of compounds is the preparation of a derivative of Arg (or another analogue of this amino acid) , which is methylated exclusively on the α-amino group. Previous attempts to make peptides containing this amino acid have involved the synthesis of derivatives of MeArg which require relatively expensive starting materials, and multi-step syntheses. For example, the process described in United States Patent Application 07/949,085 uses N-α methyl Tosyl protected Arginine as the initial starting material. Thus, Boc- eArg protected at the guanidino function with a tosyl group has been prepared starting with tosyl-arginine in a 4-step procedure. This derivative can then be incorporated into peptides by the solution phase or solid phase method. This method is very expensive and is not easily amenable to bulk preparation. Alternatively, MeArg can be introduced into peptides via a N°-phthalyl-protected Orn intermediate using the general approach described for Lys derivatives in R. M. Freidinger, J. S. Hinkle, D. S. Perlow, B. H. Arison, J " . Org. Chem. (1983), 48: 77-81, and the guanidino group introduced at a later point in the synthesis as described in Z. Tian, R. W. Roeske, Int . J. Pept . Prot . Res . (1991), 37: 425-429 and references therein. However, this procedure requires many steps resulting in an expensive process. Thus, there is a need for a process capable of providing these compounds that utilizes inexpensive, readily available starting materials and intermediates, cheaper coupling reagents, techniques for cyclizing the compound that do not require high dilution in solvents which are difficult to remove and which result in higher outputs. The present invention involves the use of a protected form of Gin which is dehydrated to give a derivative of 2-amino-4-cyano-butyric acid. Such derivatives of 2-amino-4-cyano-butyric acid have been prepared starting with Gin as described in Z. Grzonka, B. Liberek, Bull. Acad. Pol . Sci . Ser. Sci . Biol . (1969), 17: 219-22; T. Yoneta, S. Shibahara, S. Fukatsu, S. Seki, Bull . Chem. Soc . Jpn . (1978); and M. Wilchek, S. Ariely, A. Patchornik, J. Org. Chem. (1968), 33: 1258-9, and these derivatives have also been used to prepare Orn as described in I. Mezo, M. Havranek, I. Teplan, J. Benes, B. Tanacs, Acta Chim . Acad. Sci . Hung. (1975), 85: 201-13. However, derivatives of 2-amino-4- cyano-butyric acid have not been used as synthetic intermediates to produce the selective and efficient methylation of the α-amino group of Orn or Arg, nor the incorporation of these into peptides. Thus, insertion of an alkylation reaction into the reaction scheme (Gin to methyl-2-amino-4-cyano-butyric acid to N α -MeOrn) , provides a novel entree into N α -mono-alkyl derivatives of Orn and Arg. This invention involves the novel and more efficient approach to the problem of selectively methylating the α-amino group of Orn or Arg and incorporating N α -MeArg or N α -MeOrn into peptides. SUMMARY OF THF. INVENTION It is an objective of the present invention to provide processes for the preparation of platelet glycoprotein Ilb/IIIa inhibitors of Formula (I) . It is also an objective of the present invention to provide intermediate compounds (of Formulae (II, III, IV, V, and VI) useful in said processes for the preparation of platelet glycoprotein Ilb/IIIa inhibitors. Finally, it is an objective of this invention to provide processes for the preparation of said intermediate compounds. DETAILED ESΓRTPTTQN OF THE INVENTION This invention is directed to a process for the preparation of compounds of formula (I) : G> Formula (I) comprising the steps of: (a) alkylating the α-amino group of an a inonitrile of the formula: Nq OH to produce a compound of the formula (IV) : Formula(IV) and coupling with amino acid derivatives to produce a nitrile tripeptide of the formula: (b) reducing the nitrile group from the product of step (a) to form the formula: NH 2 (c) reacting the amino group of the product of step (b) with a guanylating agent of the formula: N-XX Z , to produce the formula : (d) deprotecting the carboxyl and α-amino groups of the product from step (c) to form the compound of the formula: and coupling the above formula with a carboxylic acid derivative of formula: to produce a protected linear peptide of formula: (e) removing the protecting group (G) of the product of Step (d) to produce a deprotected linear peptide of formula (III) : Formula (III) (f) cyclizing the deprotected linear peptide of Formula (III) to produce a cyclic peptide of formula (II) : _.NXX \ NH / H Formula(II) (g) then converting the Formula (II) by a series of deprotecting and/or alkylating steps to a compound of formula (I) : Formula (I) wherein : p and p* are 0 or 1; R 19 is a C 6 -C 14 saturated, partially saturated, or aromatic carbocyclic ring system or heterocyclic ring system composed of carbon atoms and at least 1- 3 heteroatoms selected from N, 0, S; all these ring systems may be optionally substituted with 0-2 R 7 ; R 17 and R 16 are independently selected from the group: hydrogen, C 1 -C 4 alkyl, optionally substituted with halogen, C 1 -C 2 alkoxy, and ll benzyl; R!5 and R 8 are independently selected from the group: 5 hydrogen, Ci-Cβ alkyl substituted with 0-2 R 8 , C2-C8 alkenyl substituted with 0-2 R 8 , C2-C8 alkynyl substituted with 0-2 R 8 , 10 C3-C8 cycloalkyl substituted with 0-2 R 8 , C6"CiO bicycloalkyl substituted with 0-2 R 8 , 15 aryl substituted with 0-2 R 13 , and a heterocylic ring system composed of 5- 10 atoms including 1-3 nitrogen, oxygen, or sulfur heteroatoms with the remaining 20 atoms being carbon, optionally substituted with 0-2 R 13 ; R 15 and R 17 can alternatively join to form a 5-7 membered carbocyclic ring 25 substituted with 0-2 R 13 ; R 18 and R 16 can alternatively join to form a 5-7 membered carbocyclic ring substituted with 0-2 R 13 ; 30 R 7 is independently selected at each occurrence from the group: phenyl, benzyl, phenethyl, phenoxy, 35 benzyloxy, halogen, hydroxy, nitro, cyano, C1-C5 alkyl, C3-C6 cycloalkyl. C3-C6 cycloalkylmethyl, C7-C10 arylalkyl, C1-C4 alkoxy, -CO2R 20 / sulfonamide, formyl, C 3 -C 6 cycloalkoxy, -OC(=0)R 20 , -C(=0)R 20 ,-OC(=0)OR 20a , 5 -OR 20 , -CH 2 OR 20 , and C 1 -C 4 alkyl optionally substituted with -NR20R21. R 8 is independently selected at each occurrence from the group: 10 =0, F, Cl, Br, I, -CF 3 , -CN, -C02R 20 , -C(=O)NR 20 R 21 , -CH 2 OR 20 , -OC(=O)R20, -CH 2 NR 20 R 21 , and -NR 2 0R 1; 15 R 13 i s independently selected at each occurrence from the group: phenyl, benzyl, phenethyl, phenoxy, benzyloxy, halogen, hydroxy, nitro, 20 cyano, C1-C5 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkylmethyl, C7-C10 arylalkyl, C1-C4 alkoxy, -CO2R 20 / sulfonamide, formyl, C 3 -C 6 cycloalkoxy, -OC(=0)R 20 , -C(=0)R 20 ,-OC(=0)OR 20a , 25 -OR 20 , -CH OR 20 , and C 1 -C 4 alkyl optionally substituted with -NR 20 R 21 ; R 20 is independently selected at each occurrence from the group: 30 H, C1-C8 alkyl, aryl, -(C1-C6 alkyl)aryl, and C3-C6 alkoxyalkyl; R 20a i s R 20, but not H . R 2 1 is independently selected at each 35 occurrence from the group: H, C1-C4 alkyl, and benzyl; R 12 is H or C1-C8 alkyl; R 2 is H, Cχ-C8 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkylmethyl, Cχ-C6 cycloalkylethyl, phenyl, phenylmethyl, CH2OH, CH2SH, CH2OCH3, CH2SCH3, CH2CH2SCH3, (CH 2 ) 3 NH 2 , (CH 2 ) 8 NHC(=NH) (NH 2 ) , or (CH 2 ) S NHR 21 , wherein s is 3-5; or R 12 and R 2 can be taken together to form -(CH2) t ~ / or -CH2SC(CH3)2- , wherein t is 2-4; R 3 is H or Ci-Ce alkyl or C1-C4 alkylphenyl; R 9 is H, Ci-Cβ alkyl; R 5 is H, Cχ-C8 alkyl; R 11 is H or Ci-Cβ alkyl; R 4 is independently selected at each occurrence from: H, Ci-Ce alkyl; C 2 -C8 alkenyl; C 2 -C 8 alkynyl; C 3 -C 8 cycloalkyl; Ci-Cβ alkyl substituted with aryl, optionally substituted with 1-2 substituents independently selected from halogen, phenyl, C 1 -C 5 alkyl, C 1 -C 5 alkoxy, N0 2 , -S (0) 0 - 2 (C 1 -C 5 alkyl), OH, N (R 22 ) 2 , CO2R 22 , CON (R 22 ) 2 or -C V F W where v = 1 to 3 and w = 1 to (2v+l ) ; C 3 -C 8 cycloalkyl ; and aryl, optionally substituted with 1-2 substituents independently selected from halogen, phenyl, C1-C5 alkyl, C1-C5 alkoxy, NO2, ' -S(0) 0-2 (Cι~ C5 alkyl), OH, N(R 22 )2/ CO2R 22 , CON(R 22 )2 or -C v Fw where v = 1 to 3 and w = 1 to (2v+l) ; C 2 -C 8 alkyl, alkenyl or alkynyl; substituted with 1-2 substituents independently selected from C 1 -C 4 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 5 alkoxy, phenoxy, benzyloxy, halogen, O 2 CN, CO 2 R 22 , CON(R 22 ) 2 , N(R 24 )COR 24 , morpholino, 2-(l- morpholino)ethoxy, N(R 22 ) 2 . N + (R 22 ) 3 , 0C0CH3, CF 3 , S(0)o-2R 22 / -CH(R 24 )OR 26 ; -CH(R 4 )OC(=0)R 25 ; -CH(R 24 )OC(=0)OR 26 ; -CH(R 24 )OC(=0)N(R 25 ) 2 ; -CH(R 24 )N(R 24 )C(=0)R 24 ; -CH(R 24 )C0 2 R 25 ; -CH(R 24 )C0N(R 2 ) 2 ; -CH(R )N(R 2 ) 2 ; IS " erein R22 is selected independently from: H, Ci-Cio alkyl, C3-C10 cycloalkyl, C4-C12 alkylcycloalkyl, aryl, -(Cχ-Cιo alkyl)aryl, or C3-CX0 alkoxyalkyl; when two R 22 groups are bonded to a single N, said R 22 groups may alternatively be taken together to form -(CH 2 ) 2 -5~ or -(CH 2 )0(CH 2 )-; R 24 is selected independently from: H, Ci-Cβ alkyl, C 3 -C 10 cycloalkyl, phenyl, or benzyl; R 25 is selected from: H; \Q> Ci-Cβ alkyl or C 3 -C 8 cycloalkyl, said alkyl or cycloalkyl being substituted with 1-2 groups independently selected from: 5 C1-C4 alkyl; C 3 -C 8 cycloalkyl; C 1 -C 5 alkoxy; aryl substituted with 0-2 groups independently selected from: 10 halogen, phenyl, C 1 -C 6 alkyl, C1-C6 alkoxy, NO 2 , -S (C 1 -C 5 alkyl), -SO(Cι-C 5 alkyl), -S0 (C_-C 5 alkyl), -OH, -N(R 22 ) 2 , -C0 R 22 , -C(=0)N(R 22 ) 2 , or -C V F W where v = 1 15 to 3 and w = 1 to (2v+l); aryl substituted with 0-2 groups independently selected from: halogen, phenyl, Ci-Cβ alkyl, Ci-Cβ alkoxy, N0 2 , -S(Cι-C 5 alkyl), -SO(Cι-C 5 20 alkyl), -SO 2 (C 1 -C 5 alkyl), -OH, -C V F W where v = 1 to 3 and = 1 to (2v+l); 25 R 26 is selected from: Ci-Cβ alkyl or C 3 -C 8 cycloalkyl, said alkyl or cycloalkyl being substituted with 1-2 groups independently selected from: 30 C 1 -C4 alkyl; C 3 -C 8 cycloalkyl; C 1 -C 5 alkoxy; aryl substituted with 0-2 groups independently selected from: 35 halogen, phenyl, Cι~Cζ alkyl, C 1 -C 6 11 alkoxy, NO 2 , -S (C 1 -C 5 alkyl), -S0(Cι-C 5 alkyl), -S0 2 (C 1 -C 5 alkyl), -OH, -N(R 22 ) , -C0 2 R 22 , -C(=0)N(R 22 )2, or -C V F W where v = 1 5 to 3 and w = 1 to (2v+l); aryl substituted with 0-2 groups independently selected from: halogen, phenyl, Ci-Cβ alkyl, Ci-Cβ alkoxy, N0 2 , -S(Cι-C 5 alkyl), -SO(Cι-C 5 10 alkyl), -SO 2 (C 1 -C 5 alkyl), -OH, -N(R 22 ) , -C0 2 R 22 , -C(=0)N(R 2 ) , or -C V F W where v = 1 to 3 and w = 1 to (2v+l); 15 R 27 is selected from: H; Ci-Cβ alkyl or C 3 -C8 cycloalkyl, said alkyl or cycloalkyl being substituted with 1-2 groups independently selected 20 from: (i) Ci-Cβ alkyl; (ii) Cχ-C 6 alkoxy; (iii) aryl substituted with 0-2 groups independently selected from: 25 halogen, phenyl, ι~Ce alkyl, Ci-Cε alkoxy, NO 2 , -S (C 1 -C 5 alkyl), -SO(Cι-C 5 alkyl), -S0 2 (C 1 -C 5 alkyl), -OH, -N(R 22 )2/ -CO2R 22 , -C(=0)N(R 22 )2/ or -C V F„ where v = 1 30 to 3 and w = 1 to (2v+l); aryl substituted with 0-2 groups independently selected from: halogen, phenyl, C 1 -C 6 alkyl, Ci-Cε alkoxy, N0 2 , -S(Cι-C 5 alkyl), -SO(Cι-C 5 35 alkyl), -S0 2 (C 1 -C 5 alkyl), -OH, -N(R 22 ) 2 , -C0 2 R 22 , -C(=0)N(R 22 ) 2 , or IS -C V F W where v = 1 to 3 and w = 1 to (2v+l); R 28 is selected from: H, C 1 -C 5 alkyl, or benzyl; R 6 is CH2C02Y; n is 1 to 4; m is 0 to 3; W and G are H or amine protecting groups and are independently selected from the group consisting of: acyl types such as formyl, trifluoroacetyl, phthalyl, and p- toluenesulfonyl; aromatic carbamate types such as benzyloxycarbonyl (Cbz) and substituted benzyloxycarbonyls, 1-(p- biphenyl)-1-methylethoxycarbonyl, and 9- fluorenylmethyloxycarbonyl (Fmoc) ; aliphatic carbamate types such as tert-butyloxycarbonyl (Boc) , ethoxycarbonyl, diisopropylmethoxycarbonyl, and allyloxycarbonyl; cyclic alkyl carbamate types such as cyclopentyloxycarbonyl and adamantyloxycarbonyl; alkyl types such as triphenylmethyl and benzyl; trialkylsilane such as trimethylsilane; and thiol containing types such as phenylthiocarbonyl and dithiasuccinoylalkyl-urethane; sulfenyl types such as O-nitrophenylsulfenyl (NPS) and 0- nitropyridylsulfenyl (NPYS); Y is H or a suitable carboxylate protecting group and can be selected from the group consisting of: alkyl esters such as C to C8 alkyl, C5 to Cβ cycloalkylalkyl and t- butyl; aryl esters such as benzyl, substituted benzyl, triphenylmethyl, 5 diphenylmethyl, pentamethylbenzy1,tetramethylbenzy1, and trimethylbenzyl; or esters which can be cleaved by acidolysis, mild base treatment or mild reductive means such as 10 trichloroethyl and phenacyl esters; other protecting groups can be CH2CH2CN, trialkylsilyl, phthalimidomethyϊ, anthrylmethyl, phenylfluorenyl, 4-picolyl and phenacyl; 15 XX is H or a suitable amine protecting group and is selected from the group consisting of: acyl types such as formyl, trifluoroacetyl, phthalyl, and p-toluenesulfonyl; aromatic 20 carbamate types such as benzyloxycarbonyl (Cbz) and substituted benzyloxycarbonyls, 1- (p-biphenyl)-1-methylethoxycarbonyl, and 9- fluorenylmethyloxycarbonyl (Fmoc) ; aliphatic carbamate types such as tert-butyloxycarbonyl 25 (Boc) , ethoxycarbonyl, diisopropylmethoxycarbonyl, and allyloxycarbonyl; cyclic alkyl carbamate types such as cyclopentyloxycarbonyl and adamantyloxycarbonyl; alkyl types such as 30 triphenylmethyl and benzyl; trialkylsilane such as trimethylsilane; and thiol containing types such as phenylthiocarbonyl and dithiasuccinoylalkyl-urethane; sulfenyl types such as O-nitrophenylsulfenyl (NPS) , 35 nitropyridylsulfenyl (NPYS) , 2,3,6-trimethyl- 4-methoxybenzenesulfonamide ( tr-NR2), 2,4,6- trimethoxybenzenesulfonamide (Mtb-NR2) , 2,6- dimethyl-4-methoxybenzenesulfonamide (Mds- NR2) pentamethylbenzenesulfonamide (Pme-NR2), 2,3,5, 6-tetramethyl-4-methoxybenzene- sulfonamide ( te-NR2) , 4-methoxybenzene- sulfonamide ( bs-NR2) , 2,4,6- trimethylbenzenesulfonamide (Mts-NR2), 2,6- dimethoxy-4-methoxybenzenesulfonamide (i ds- NR2), and 2,2,5,7,8-Pentamethylchroman-6- sulfonamide (Pmc-NR2) ; and Z is a leaving group such as Sθ3~, S-alkyl, 0- alkyl or an O-substituted derivative of hydroxylamine. The present invention also provides for the process for the preparation of compounds of Formula Formula (I) comprising the steps of: (a) alkylating an aminonitrile of the formula: Nq OH to produce a compound of the formula (IV) Formula(IV) converting formula (IV) above through a series of deprotecting steps and coupling with amino acid derivatives to produce a protected nitrile tripeptide of the formula (V) : Formula(V) (b) coupling formula (V) with a carboxylic acid derivative of the formula: T2-- wherein G is a suitable amine protecting group, to produce a protected linear peptide of formula: (c) removing the protecting groups of the product of Step (b) to produce a deprotected linear peptide of formula: (d) cyclizing the deprotected linear peptide of the product of step (c) to produce a cyclic peptide of formula (VI) : H Formula (VI) (e) reducing the nitrile from the product of step (d) to form the formula: NH 2 H (f) reacting the product of step (e) with a guanylating agent of the formula: , leading directly to a compound of Formula I, or via a series of deprotecting and/or alkylating steps converting to a compound of formula (I) : Formula (I) wherein R 1 to R 28 and all other groups are as defined above . In a preferred embodiment, the above described processes provide compounds of formula (I ) wherein : n is 3; R!9 is selected from: IS R 15 and R 18 are independently selected from H, Cχ-C4 alkyl, phenyl, benzyl, phenyl- (C2-C4)alkyl, C 1 -C 4 alkoxy; R 17 and R 16 are independently H or C 1 -C 4 alkyl; R 7 is H, Ci-Cβ alkyl, phenyl, halogen, or C 1 -C 4 alkoxy; R 11 is H or C 1 -C 3 alkyl; R 12 is H or CH3; R 3 is H, Cχ-C8 alkyl; R 9 is H, C 1 -C 3 alkyl; R 5 is H, C 1 -C 3 alkyl; R 4 is selected independently from: H, Ci-Cβ alkyl; C 2 -C 8 alkenyl; C 2 -C 8 alkynyl; C 3 -C 8 cycloalkyl; Ci-Cβ alkyl substituted with aryl, optionally substituted with 1-2 substituents independently selected from halogen, phenyl, C 1 -C 5 alkyl, C 1 -C 5 alkoxy, N0 , -S(0) 0 - 2 (C 1 -C 5 alkyl), OH, N(R 22 ) 2 , C0 R 22 , CON(R 2 )2 or -C V F W where v = 1 to 3 and w = 1 to (2v+l); C 3 -C 8 cycloalkyl; and aryl, optionally substituted with 1-2 substituents independently selected from halogen, phenyl, C 1 -C5 alkyl, C 1 -C5 alkoxy, NO2, -S (0) 0-2 (C_-C 5 alkyl), OH, N(R 22 ) 2 , C0 2 R 22 , CON(R 22 ) 2 or -C V F W where v = 1 to 3 and w = 1 to (2v+l) ; C2-C8 alkyl, alkenyl or alkynyl; substituted with 1-2 substituents independently selected from C 1 -C 4 alkyl, C3-C8 cycloalkyl, C 1 -C5 alkoxy, phenoxy, benzyloxy, halogen, NO2, CN, CO2R 22 , C0N(R 22 ) 2 , N(R 24 )COR 24 , morpholino, 2-(l- morpholino) ethoxy, N(R 22 ) 2 , N+(R 2 ) 3 , OCOCH3, CF 3 , S ( O) 0 -2R 22a ; -CH(R 24 )OR 26 ; -CH(R 2 )OC(=0)R 25 ; -CH(R 24 )OC(=0)OR 26 ; -CH (R 24 ) OC (=0)N (R 25 ) ; -CH(R 24 )C0 2 R 25 ; In the most preferred embodiment, the above- described processes provide compounds of formula (I) wherein: R 2 is H or C 1 -C 4 alkyl; R 5 , R 9 , R 16 , R 17 and R 18 are H; R 11 and R 12 are H or CH3; R 15 is H, Cχ-C4 alkyl, phenyl, benzyl, or phenyl- (C2-C4)alkyl; and R 3 is H or C 1 -C 3 alkyl; R 4 is selected independently from: H, -CH(R 24 )0C(=0)R 25 , -CH(R 24 )0C(=0)0R 26 , -CH 2 OC(=0)N(R 25 ) 2 , -CH CH 2 N(R 2 ) 2 , -CH(R 24 )C0 2 R 25 , and wherein R 24 is selected independently from: H, Ci-Cβ alkyl, phenyl, or benzyl; and R27 is selected from: C 1 -C 5 alkyl, benzyl or phenyl. 18 In the specifically preferred embodiment, the above described process provides compounds of formula (I) wherein: n is 3; p is 0, p' is 1; R!9 is phenyl R 5 , R 9 , R 11 , and R 12 are H; R 2 is ethyl; R 3 is methyl; and R^ is selected independently from: H, -CH(R 24 )OC(=0)R 25 , -CH(R 24 )OC(=0)OR 26 , and ; wherein R 24 is C 1 -C 4 linear alkyl or H; and R 27 is C 1 -C 4 alkyl, benzyl, or phenyl This invention also provides a process for the preparation of an intermediate compound of formula (IV) : Formula (IV) comprising the steps of: (a) dehydrating the carboxamide group of the formula: H 2 N to the corresponding nitrile to produce the formula: NC (b) then selectively alkylating the product of step (a) at the α-amino group using a suitable alkylating agent to produce formula (IV) above, wherein: R 3 is H or Ci-Cβ alkyl; m is 0 to 3; and c- W is a suitable amine protecting group and is selected from the group consisting of: acyl types such as formyl, trifluoroacetyl, phthalyl, and p- toluenesulfonyl; aromatic carbamate types such as benzyloxycarbonyl (Cbz) and substituted benzyloxycarbonyls, 1- (p-biphenyl)-l- methylethoxycarbonyl, and 9- fluorenylmethyloxycarbonyl (Fmoc) ; aliphatic carbamate types such as tert-butyloxycarbonyl (Boc) , ethoxycarbonyl, diisopropylmethoxycarbonyl, and allyloxycarbonyl; cyclic alkyl carbamate types such as cyclopentyloxycarbonyl and adamantyloxycarbonyl; alkyl types such as triphenylmethyl and benzyl; trialkylsilane such as trimethylsilane; and thiol containing types such as phenylthiocarbonyl and dithiasuccinoylalkyl- urethane. Further this invention provides a process for the preparation of an intermediate compound of the formula: H Formula (II) 3i comprising the steps of cyclizing a compound of formula (III) : Formula (III) wherein : n is 1 to 4; W erein : p and p ' are 0 or 1; R 19 is a C 6 ~Ci 4 saturated, partially saturated, or aromatic carbocyclic ring system or heterocyclic ring system composed of carbon atoms and at least 1- 3 heteroatoms selected from N, 0, S; all these ring systems may be optionally substituted with 0-2 R 7 ; R 17 and R 16 are independently selected from the group: hydrogen, 5 C 1 -C 4 alkyl, optionally substituted with halogen, C 1 -C 2 alkoxy, and benzyl; 10 R 1 ^ and R 18 are independently selected from the group: hydrogen, Cχ-Cβ alkyl substituted with 0-2 R 8 , 15 C2-C8 alkenyl substituted with 0-2 R 8 , C2-C8 alkynyl substituted with 0-2 R 8 , C3-C8 cycloalkyl substituted with 0-2 R 8 , C6-C10 bicycloalkyl substituted with 0-2 20 R 8 , aryl substituted with 0-2 R 13 , and a heterocylic ring system composed of 5- 25 10 atoms including 1-3 nitrogen, oxygen, or sulfur heteroatoms with the remaining atoms being carbon, optionally substituted with 0-2 R 13 ; 30 R 15 and R 17 can alternatively join to form a 5-7 membered carbocyclic ring substituted with 0-2 R 13 ; R 18 and R 16 can alternatively join to form a 5-7 membered carbocyclic ring substituted with 0-2 R 13 ; 5 R 7 is independently selected at each occurrence from the group: phenyl, benzyl, phenethyl, phenoxy, benzyloxy, halogen, hydroxy, nitro, 10 cyano, C1-C5 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkylmethyl, C7-C10 arylalkyl, C1-C4 alkoxy, -CO2R 20 , sulfonamide, formyl, C 3 -C 6 cycloalkoxy, -OC(=0)R 20 , -C(=0)R 20 ,-OC(=0)OR 0a , 15 -OR 20 , -CH 2 OR 20 , and C 1 -C 4 alkyl optionally substituted with - R 2 0R ; R 8 is independently selected at each occurrence from the group: 20 =0, F, Cl, Br, I, -CF 3 , -CN, -Cθ2R 20 , -C(=O)NR 20 R 21 , -CH 2 OR 20 , -OC(=O)R20, -CH 2 NR 20 R 21 , and -NR 20 R 21 ; 25 R 3 is independently selected at each occurrence from the group: phenyl, benzyl, phenethyl, phenoxy, benzyloxy, halogen, hydroxy, nitro, 30 cyano, Cχ-C5 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkylmethyl, C7-C 0 arylalkyl, Cχ-C4 alkoxy, -CO2R 20 , sulfonamide, formyl, C 3 -C 6 cycloalkoxy, -OC(=0)R 20 , -C(=0)R 20 ,-OC(=0)OR 20a , -OR 20 , -CH 2 OR 20 , and C 1 -C 4 alkyl optionally substituted with -NR 0 R 21 ; R 20 is independently selected at each occurrence from the group: H, Cχ-C8 alkyl, aryl, -(C1-C6 alkyl)aryl, and C3-C6 alkoxyalkyl; R 20a is R20, bu t not H; R 21 is independently selected at each occurrence from the group: H, Cχ-C4 alkyl, and benzyl; R 12 is H or C1-C8 alkyl; R 2 is H, Cχ-C8 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkylmethyl, Cχ-C6 cycloalkylethyl, phenyl, phenylmethyl, CH2OH, CH2SH, CH2OCH3, CH2SCH3, CH2CH2SCH3, (CH 2 ) 3 NH 2 , (CH 2 ) S NHC(=NH) (NH 2 ) , or (CH 2 ) S NHR 21 , wherein s is 3-5; or R 12 and R 2 can be taken together to form -(CH2)t~ / or -CH 2 SC(CH3) 2 ~ , wherein t is 2-4; R 3 is H or Ci-Cβ alkyl; R 9 is H, Ci-Cβ alkyl; R 5 is H, Ci-Cβ alkyl; R 11 is H or Ci-Cβ alkyl; R6 is CH2CO2Y; Y is a suitable carboxylate protecting group and can be selected from the group consisting of: alkyl esters such as Ci to Cδ alkyl, C5 to Cβ cycloalkylalkyl and t- butyl; aryl esters such as benzyl, substituted benzyl, triphenylmethyl, diphenylmethy1, pentamethylbenzy1,tetramethylbenzy1, and trimethylbenzyl; or esters which can be cleaved by acidolysis, mild base treatment or mild reductive means such as trichloroethyl and phenacyl esters; other protecting groups can be CH2CH2CN, trialkylsilyl, phthalimidomethyl, anthrylmethyl, phenylfluorenyl, 4-picolyl and phenacyl; and XX is H or a suitable amine protecting group and is selected from the group consisting of: acyl types such as formyl, trifluoroacetyl, phthalyl, and p-toluenesulfonyl; aromatic carbamate types such as benzyloxycarbonyl (Cbz) and substituted benzyloxycarbonyIs, 1- (p-biphenyl)-1-methylethoxycarbonyl, and 9- fluorenylmethyloxycarbonyl (Fmoc) ; aliphatic carbamate types such as tert-butyloxycarbonyl (Boc) , ethoxycarbonyl, diisopropylmethoxycarbonyl, and allyloxycarbonyl; cyclic alkyl carbamate types such as cyclopentyloxycarbonyl and adamantyloxycarbonyl; alkyl types such as triphenylmethyl and benzyl; trialkylsilane such as trimethylsilane; and thiol containing types such as phenylthiocarbonyl and dithiasuccinoylalkyl-urethane; sulfenyl types such as O-nitrophenylsulfenyl (NPS) , 3 nitropyridylsulfenyl (NPYS) , 2,3, 6-trimethyl- 4-methoxybenzenesulfonamide (Mtr-NR2), 2,4,6- trimethoxybenzenesulfonamide ( tb-NR2) , 2,6- dimethyl-4-methoxybenzenesulfonamide ( ds- R2)/ pentamethylbenzenesulfonamide (Pme-NR2) , 2,3,5, 6-tetramethyl-4-methoxybenzene- sulfonamide (Mte-NR2) , 4-methoxybenzene- sulfonamide (Mbs-NR2) , 2,4,6- trimethylbenzenesulfonamide (Mts-NR2) , 2,6- dimethoxy-4-methoxybenzenesulfonamide (iMds- NR2) and 2,2,5,7,8-Pentamethylchroman-6- sulfonamide (Pmc-NR2) . In a preferred embodiment, the above described process provides an intermediate compound of formula (II) wherein: n is 3; - 1 9 is selected from: R 15 and R 18 are independently selected from H, Cχ-C4 alkyl, phenyl, benzyl, phenyl-(C2-C4)alkyl, C 1 -C 4 alkoxy; R 17 and R 16 are independently H or C 1 -C 4 alkyl; R 7 is H, Ci-Cβ alkyl, phenyl, halogen, or C 1 -C 4 alkoxy; R 11 is H or C 1 -C 3 alkyl; R 12 is H or CH3; R 9 is H, C 1 -C 3 alkyl; R 5 is H, C 1 -C 3 alkyl; and XX is selected from the group consisting of: t-Boc, acyl, phthalyl, o- nitrophenylsulfenyl, Cbz, Fmoc, and fluorenylphenyl. In a more preferred embodiment, the above- described process provides intermediate compounds of formula (II) wherein: R 2 is H or Cχ-C4 alkyl; R5, R9, R16 / R 17 and R 18 are H; R 11 , and R 12 are H or CH3; or R 2 and R 12 together are -(CH2)3~ R 15 is H, Cχ-C4 alkyl, phenyl, benzyl, or phenyl-(C2-C4)alkyl; and R 3 is H or C 1 -C 3 alkyl. The above-described process specifically provides intermediate compounds of formula (II) wherein: p is 0, p' is 1; n is 3; R 19 is phenyl; R 5 , R 9 , R 11 , and R 12 are H; R 2 is ethyl; R 3 is methyl; R 6 is CH2~OBn, CH2~OtBu, or CH2~0-tBoc; and XX is Cbz or Boc. This invention also provides intermediate compounds useful in the claimed processes for the preparation of compounds of formula (I) . Said intermediate compounds have formulae: Formula (II) # Formula (III) Formula (IV) Formula (V) , and CN / H Formula (VI) wherein : \ p and p 1 are 0 or 1; R 19 is a C 6 ~Ci 4 saturated, partially saturated, or aromatic carbocyclic ring system or heterocyclic ring system composed of carbon atoms and at least 1- ' 3 heteroatoms selected from N, 0, S; all these ring systems may be optionally substituted with 0-2 R 7 ; R 17 and R 16 are independently selected from the group: hydrogen, C 1 -C 4 alkyl, optionally substituted with halogen, C 1 -C 2 alkoxy, and benzyl; R 1 ^ and R 18 are independently selected from the group: hydrogen, Cχ-C8 alkyl substituted with 0-2 R 8 , C2-C8 alkenyl substituted with 0-2 R 8 , C2-C8 alkynyl substituted with 0-2 R 8 , C3-C8 cycloalkyl substituted with 0-2 R 8 , C6~Ci0 bicycloalkyl substituted with 0-2 R 8 aryl substituted with 0-2 R 13 , and a heterocylic ring system composed of 5- 10 atoms including 1-3 nitrogen, oxygen, 5 or sulfur heteroatoms with the remaining atoms being carbon, optionally substituted with 0-2 R 13 ; R 15 and R 17 can alternatively join to form a 10 5-7 membered carbocyclic ring substituted with 0-2 R 13 ; R 18 and R 16 can alternatively join to form a 5-7 membered carbocyclic ring 15 substituted with 0-2 R 13 ; R 7 is independently selected at each occurrence from the group: 20 phenyl, benzyl, phenethyl, phenoxy, benzyloxy, halogen, hydroxy, nitro, cyano, Cχ-C5 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkylmethyl, C7-C10 arylalkyl, C1-C4 alkoxy, -CO2R 20 / 25 sulfonamide, formyl, C 3 -C 6 cycloalkoxy, -OC(=0)R 20 , -C(=0)R 20 ,-OC(=0)OR 20a , -OR 20 , -CH 2 OR 20 , and C 1 -C 4 alkyl optionally substituted with -NR 20 R 21 ; 30 R 8 is independently selected at each occurrence from the group: =0, F, Cl, Br, I, -CF 3 , -CN, -CO2R 20 , -C(=O)NR 20 R 21 , -CH 2 OR 20 , -OC(=O)R20, 35 -CH 2 NR 20 R 21 , and -NR 20 R 21 ; R 13 is independently selected at each occurrence from the group: phenyl, benzyl, phenethyl, phenoxy, benzyloxy, halogen, hydroxy, nitro, cyano, C1-C5 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkylmethyl, C7-C10 arylalkyl, C1-C4 alkoxy, -CO2R 20 , sulfonamide, formyl, C 3 -C 6 cycloalkoxy, -OC(=0)R 20 , -C(=0)R 20 ,-OC(=0)OR 20a , -OR 20 , -CH 2 OR 20 , and C 1 -C 4 alkyl optionally substituted with -NR 2 0R 21 ; R 20 is independently selected at each occurrence from the group: H, Cχ-C8 alkyl, aryl, -(Cχ-C6 alkyl)aryl, and C3-C6 alkoxyalkyl; R 20a is R 20 ' but not H; R 21 is independently selected at each occurrence from the group: H, C1-C4 alkyl, and benzyl; R 12 is H or C1-C8 alkyl; R 2 is H, Cχ-Cβ alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkylmethyl, C1-C6 cycloalkylethyl, phenyl, phenylmethyl, CH2OH, CH2SH, CH2OCH3, CH2SCH3, CH2CH2SCH3, (CH 2 ) S NH 2 , (CH 2 ) S NHC(=NH) (NH 2 ) , or (CH 2 ) S NHR 21 , wherein s is 3-5; or R 12 and R 2 can be taken together to form -(CH2) t ~ / or -CH 2 SC(CH 3 ) 2 ~ 1 wherein t is 2-4; R 3 is H or Ci-Cβ alkyl; R 9 is H, C1-C8 alkyl; R 5 is H, Cι-C8 alkyl; R 11 is H or Cι-C 8 alkyl; R 6 is CH2C02Y or CH2CO2R 4 ; R4 is independently selected at each occurrence from: H, Ci-Cβ alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, Ci-Cβ alkyl substituted with aryl, optionally substituted with 1-2 substituents independently selected from halogen, phenyl, C 1 -C 5 alkyl, C 1 -C 5 alkoxy, NO 2 , -S (0) 0 - 2 (C 1 -C 5 alkyl), OH, N(R 22 )2, CO2R 22 , CON(R 2 ) 2 or -C V F W where v = 1 to 3 and w = 1 to (2v+l) ; C 3 -C 8 cycloalkyl, or aryl, optionally substituted with 1-2 substituents independently selected from halogen, phenyl, C 1 -C 5 alkyl, C 1 -C 5 alkoxy, NO2 -S (0) 0-2 (C 1 -C5 alkyl), OH, N(R 22 )2, CO2R 22 , CON(R 22 )2 or -C V F W where v = 1 to 3 and w = 1 to (2v+l) ; C2-C8 alkyl, alkenyl or alkynyl; substituted with 1-2 substituents independently selected from C 1 -C 4 alkyl, C3-C8 cycloalkyl, C 1 -C5 alkoxy, phenoxy, benzyloxy, halogen, NO2. CN, CO2R 22 , CON(R 2 ) 2 , N(R 24 )COR 24 , morpholino, 2-(l- morpholino) ethoxy, N(R 22 ) 2 , N + (R 22 ) 3 , 0C0CH3, CF 3 , S(O) 0 -2R 22 ; CH(R 24 )OR 26 , CH(R 24 )OC(=0)R 25 , CH(R 24 )OC(=0)OR 2 6, CH(R 24 )OC(=0)N(R 25 ) 2 , CH(R 24 )N(R 24 )C(=0)R 24 , CH(R 2 )C0 2 R 25 , CH(R 24 )N(R 22 )2, S erein 5 R 22 is selected independently from: H, Cχ-Cιo alkyl, C3-C10 cycloalkyl, " C4-C12 alkylcycloalkyl, aryl, -(Cχ-Cιo alkyl)aryl, or C3-C10 alkoxyalkyl; 10 when two R 22 groups are bonded to a single N, said R 22 groups may alternatively be taken together to form -(CH 2 )2-5~ or -(CH 2 )0(CH 2 )-; 15 R 24 is selected independently from: H, Ci-Cβ alkyl, C 3 -C 10 cycloalkyl, phenyl, or benzyl; R25 i s selected from: 20 H; Cχ-C 8 alkyl or C 3 -C 8 cycloalkyl, said alkyl or cycloalkyl being substituted with 1-2 groups independently selected from: 25 C1-C4 alkyl; C 3 -C 8 cycloalkyl; C 1 -C 5 alkoxy; aryl substituted with 0-2 groups independently selected from: halogen, phenyl, C 1 -C 6 alkyl, Ci-Ce alkoxy, NO 2 , -S (C 1 -C 5 alkyl), -SO(Cι-C 5 alkyl), -S0 2 (C 1 -C 5 alkyl), -OH, -N(R 2 ) 2 , -C0 2 R 22 , 5 -C(=0)N(R 2 ) 2 , or -C V F W where v = 1 to 3 and w = 1 to (2v+l); aryl substituted with 0-2 groups independently selected from: halogen, phenyl, Ci-Cβ alkyl, Ci-Cβ alkoxy, 10 NO 2 , -S(Cι-C5 alkyl), -SO(Cι-C 5 alkyl), -S0 2 (C 1 -C5 alkyl), -OH, -N(R 22 ) 2 , -C0 R 22 , -C(=0)N(R 22 ) 2 , or -C V F W where v = 1 to 3 and w = 1 to (2v+l); 15 R 26 is selected from: Ci-Ce alkyl or C 3 -C 8 cycloalkyl, said alkyl or cycloalkyl being substituted with 1-2 groups independently selected 20 from: C 1 -C 4 alkyl; C 3 -C 8 cycloalkyl; C 1 -C 5 alkoxy; aryl substituted with 0-2 groups 25 independently selected from: halogen, phenyl, Ci-Cβ alkyl, C 1 -C 6 alkoxy, NO 2 , -S(C 1 -C 5 alkyl), -SO(Cι-C 5 alkyl), -S0 2 (C 1 -C 5 alkyl), -OH, -N(R 22 ) 2 , -C0 2 R 22 , 30 -C(=0)N(R 2 ) 2 , or -C V F W where v = 1 to 3 and w = 1 to (2v+l); aryl substituted with 0-2 groups independently selected from: halogen, phenyl, Ci-Cε alkyl, Ci-Cβ alkoxy, 35 N0 2 , -S(Cι-C 5 alkyl), -S0(Cι-C 5 alkyl), -S0 2 (C 1 -C5 alkyl), -OH, 41 -N(R 2 ) 2 , -C0 2 R 22 , -C(=0)N(R 22 ) 2 , or -C V F W where v = 1 to 3 and w = 1 to (2v+l); R 27 is selected from: H Ci-Cβ alkyl or C 3 -C 8 cycloalkyl, said alkyl or cycloalkyl being substituted with 1-2 groups independently selected from: (i) Ci-Cβ alkyl; (ii) Cχ-C 6 alkoxy; (iii) aryl substituted with 0-2 groups independently selected from: halogen, phenyl, Ci-Cβ alkyl, Ci-Cε alkoxy, NO 2 -S(C 1 -C 5 alkyl), -SO(Cι-C 5 alkyl), -S0 (C 1 -C 5 alkyl), -OH, -N(R 22 ) 2 , -C0 R 22 , -C(=0)N(R 2 )2, or -C V F W where v = 1 to 3 and w = 1 to (2v+l); aryl substituted with 0-2 groups independently selected from: halogen, phenyl, Ci-Cβ alkyl, C 1 -C 6 alkoxy, NO 2 , -S(Cι-C 5 alkyl), -SO(Cι-Cs alkyl), -SO 2 (C 1 -C 5 alkyl), -OH, -N(R 22 ) , -CO2R 22 , -C(=0)N(R 22 ) 2 , or -C V F W where v = 1 to 3 and w = 1 to (2v+l); R 28 is selected from: H, C 1 -C 5 alkyl, or benzyl; n is 1 to 4; m is 0 to 3; Y is H or a suitable carboxylate protecting group and can be selected from the group consisting of: alkyl esters such as C to C8 alkyl, C5 to C8 cycloalkylalkyl and t- butyl; aryl esters such as benzyl, substituted benzyl, triphenylmethyl, diphenylmethy1, pentamethylbenzy1,tetramethylbenzy1, and trimethylbenzyl; or esters which can be cleaved by acidolysis, mild base treatment or mild reductive means such as trichloroethyl and phenacyl esters; other protecting groups can be CH2CH2CN, trialkylsilyl, phthalimidomethyl, anthrylmethyl, phenylfluorenyl, 4-picolyl and phenacyl; W is H or an amine protecting group and is selected from the group consisting of: acyl types such as formyl, trifluoroacetyl, phthalyl, and p- toluenesulfonyl; aromatic carbamate types such as benzyloxycarbonyl (Cbz) and substituted benzyloxycarbonyls, l-(p- biphenyl)-1-methylethoxycarbonyl, and 9- fluorenylmethyloxycarbonyl (Fmoc) ; aliphatic carbamate types such as tert-butyloxycarbonyl (Boc) , ethoxycarbonyl, diisopropylmethoxycarbonyl, and allyloxycarbonyl; cyclic alkyl carbamate types such as cyclopentyloxycarbonyl and adamantyloxycarbonyl; alkyl types such as triphenylmethyl and benzyl; trialkylsilane such as trimethylsilane; and thiol containing types such as phenylthiocarbonyl and dithiasuccinoylalkyl-urethane; sulfenyl types such as 0-nitrophenylsulfenyl (NPS) and nitropyridylsulfenyl (NPYS) ; and XX is H or a suitable amine protecting group and is 5 selected from the group consisting of: acyl types such as formyl, trifluoroacetyl, • phthalyl, and p-toluenesulfonyl; aromatic carbamate types such as benzyloxycarbonyl (Cbz) and substituted benzyloxycarbonyls, 1- 10 (p-biphenyl)-l-methylethoxycarbonyl, and 9- fluorenylmethyloxycarbonyl (Fmoc) ; aliphatic carbamate types such as tert-butyloxycarbonyl (Boc) , ethoxycarbonyl, diisopropylmethoxycarbonyl, and 15 allyloxycarbonyl; cyclic alkyl carbamate types such as cyclopentyloxycarbonyl and adamantyloxycarbonyl; alkyl types such as triphenylmethyl and benzyl; trialkylsilane such as trimethylsilane; and thiol containing 20 types such as phenylthiocarbonyl and dithiasuccinoylalkyl-urethane; sulfenyl types such as O-nitrophenylsulfenyl (NPS), nitropyridylsulfenyl (NPYS), 2,3, 6-trimethyl- 4-methoxybenzenesulfonamide (Mtr-NR2) , 2,4,6- 25 tri ethoxybenzenesulfonamide (Mtb-NR2), 2,6- dimethyl-4-methoxybenzenesulfonamide (Mds- NR2) pentamethylbenzenesulfonamide (Pme-NR2) , 2,3,5, 6-tetramethyl-4-methoxybenzene- sulfonamide (Mte-NR2)/ 4-methoxybenzene- 30 sulfonamide (Mbs-NR2) 2,4,6- trimethylbenzenesulfonamide (Mts-NR2) , 2,6- dimethoxy-4-methoxybenzenesulfonamide (i ds- NR2A and 2, 2 , 5, 1 , 8-Pentamethylchroman-6- . sulfonamide (?mc-NR2) . 35 Preferred intermediate compounds of formulae II, III, IV and V are those wherein: W and XX are independently Cbz, t-Boc; R 19 is selected from: R 15 and R 18 are independently selected from H, C1-C4 alkyl, phenyl, benzyl, phenyl-(C2-C4)alkyl, C 1 -C 4 alkoxy; R 17 and R 16 are independently H or C 1 -C 4 alkyl; R 7 is H, Ci-Cβ alkyl, phenyl, halogen, or Cr C 4 alkoxy; R 11 is H or C 1 -C 3 alkyl; R 12 is H or CH3 ; R 9 is H, C1-C3 alky l ; R 5 is H, C1-C3 alkyl; R 4 is selected from: H, C_-Cβ alkyl, C 2 -C 8 alkenyl, C 2 -C8 alkynyl, C 3 -C 8 cycloalkyl, Ci-Cβ alkyl substituted with aryl, optionally substituted with 1-2 substituents independently selected from halogen, phenyl, C 1 -C5 alkyl, C 1 -C5 alkoxy, NO2, -S (0) 0-2 (C1-C5 alkyl), OH, N(R 2 ) 2 , C0 2 R 22 , C0N(R 22 ) 2 or -C V F W where v = 1 to 3 and w = 1 to (2v+l); C3-C8 cycloalkyl; and aryl, optionally substituted with 1-2 substituents independently selected from halogen, phenyl, C 1 -C 5 alkyl, C 1 -C 5 alkoxy, NO2, -S (0)0-2 (C 1 -C 5 alkyl), OH, N(R 22 ) 2 , CO2R 22 , CON(R 22 ) 2 or -C V F W where v = 1 to 3 and w = 1 to (2v+l) ; C 2 -C 8 alkyl, alkenyl or alkynyl; substituted with 1-2 substituents independently selected from C 1 -C 4 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 5 alkoxy, phenoxy, benzyloxy, halogen, NO2 CN, CO 2 R 22 , C0N(R 22 ) 2 , N(R 24 )COR 24 , morpholino, 2-(l- morpholino)ethoxy, N(R ) , N + (R 22 )3/ 0C0CH3, -CH(R 2 )0R 26 , 5D- -CH(R 24 )0C(*=0)R 25 , -CH(R 24 )0C(=0)0R 26 , -CH(R 24 )OC(=0)N(R 25 ) 2 , -CH(R 24 )C0 R 25 , m is 2, and n is 3. Most preferred intermediate compounds of formulae II, IV and V are those preferred compounds wherein: R 2 is C1-C4 alkyl; R 5 , R 9 , R 16 , R 17 and R 18 are H; R 11 , and R 12 , are H or CH3; R 15 is H, C1-C4 alkyl, phenyl, benzyl, or phenyl-(C2-C4)alkyl; R 3 is H or C 1 -C 3 alkyl; R 4 is selected from: H, -CH(R 24 )OC(=0)R 25 ' -CH(R 24 )0C(=0)0R 26 , -CH 2 OC(=0)N(R 2 5) 2 , -CH CH 2 N(R 22 )2, -CH(R 24 )C0 R 25 , and wherein R 24 is H, Ci-Cβ alkyl, phenyl, or benzyl; R 27 is C 1 -C 5 alkyl, benzyl or phenyl; m is 2, and n is 3. Specifically preferred compounds of formulae II, IV, and V are those wherein: p is 0, p' is 1; R 19 is phenyl R 5 , R 9 , R 11 , R 12 , and R 14 are H; R 2 is ethyl; R 3 is methyl; m is 2, and n is 3 R 6 is CH2~OBn, CH2~OtBu, or CH2~0-tBoc; R 4 is selected from: H, -CH(R 24 )OC(=0)R 25 , -CH(R 24 )OC(=0)OR 26 ' wherein R 24 is C 1 -C 4 linear alkyl or H; R 27 is C 1 -C 4 alkyl, benzyl, or phenyl; and XX is Cbz or Boc. The compounds of Formula (I) are described in copending, commonly assigned U.S. Patent Application: Attorney Docket No. BP 6543-B, inventors: DeGrado et al., and filed on the same day as this application, and which is hereby incorporated by reference. The compounds herein described may have stereogenic centers. Unless otherwise indicated, all chiral, diastereomeric and racemic forms are included in the present invention. Many geometric isomers of olefins, C=N double bonds, and the like can also be present in the compounds described herein, and all such stable isomers are contemplated in the present invention. Two distinct isomers (cis and trans) of the peptide bond are known to occur; both can also be present in the compounds described herein, and all such stable isomers are contemplated in the present invention. Unless otherwise specifically noted, the L-isomer of the amino acid is the preferred stereomer of the present invention. The D and L-isomers of a particular amino acid are designated herein using the conventional 3- letter abbreviation of the amino acid, as indicated by the following examples: D-Leu, or L-Leu. When any variable (for example, R 1 through R 8 , m, n, p, W, Y, etc.) occurs more than one time in any constituent or in any formula, its definition on each occurrence is independent of its definition at every other occurrence. Also, combinations of substituents and/or variables are permissible only if such combinations result in stable compounds. As used herein, "alkyl" is intended to include both branched and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms; "alkoxy" represents an alkyl group of indicated number of carbon atoms attached through an oxygen bridge; "cycloalkyl" is intended to include saturated ring groups, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl; and "biycloalkyl" is intended to include saturated bicyclic ring groups such as [3.3.0]bicyclooctane, [4.3.O.bicyclononane, [4.4.O.bicyclodecane (decalin) , [2.2.2]bicyclooctane, and so forth. "Alkenyl" is intended to include hydrocarbon chains of either a straight or branched configuration and one or more unsaturated carbon-carbon bonds which may occur in any stable point along the chain, such as ethenyl, propenyl and the like; and "alkynyl" is intended to include hydrocarbon chains of either a straight or branched configuration and one or more triple carbon-carbon bonds which may occur in any stable point along the chain, such as ethynyl, propynyl and the like. "Halo" or "halogen" as used herein refers to fluoro, chloro, bromo and iodo; and "counterion" is used to represent a small, negatively charged species such as chloride, bromide, hydroxide, acetate, sulfate and the like. As used herein, "aryl" is intended to mean phenyl or naphthyl; "carbocyclic" is intended to mean any G stable 5- to 7- membered monocyclic or bicyclic or 7- to 14-membered bicyclic or tricyclic carbon ring, any of which may be saturated, partially unsaturated, or aromatic. Examples of such carbocyles include, but are not limited to cyclopentyl, cyclohexyl, phenyl, biphenyl, naphthyl, indanyl or tetrahydronaphthyl (tetralin) . As used herein, the term "heterocycle" or "heterocyclic ring system" is intended to mean a stable 5- to 7- membered monocyclic or bicyclic or 7- to 10- membered bicyclic heterocyclic ring which may be saturated, partially unsaturated, or aromatic, and which consists of carbon atoms and from 1 to 3 heteroatoms selected from the group consisting of N, 0 and S and wherein the nitrogen and sulfur heteroatoms may optionally be oxidized, and the nitrogen may optionally be quaternized, and including any bicyclic group in which any of the above-defined heterocyclic rings is fused to a benzene ring. The heterocyclic ring may be attached to its pendant group at any heteroatom or carbon atom which results in a stable structure. The heterocyclic rings described herein may be substituted on carbon or on a nitrogen atom if the resulting compound is stable. Examples of such heterocycles include, but are not limited to, pyridyl, pyrimidinyl, furanyl, thienyl, pyrolyl, pyrazolyl, imidazolyl, tetrazolyl, benzofuranyl, benzothiophenyl, indolyl, indolenyl, quinolinyl, isoquinolinyl or benzimidazolyl, piperidinyl, 4-piperidonyl, pyrrolidinyl, 2- pyrrolidonyl, pyrolinyl, tetrahydrofuranyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl or octahydroisoquinolinyl. By "stable compound" or "stable structure" is meant herein a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and formulation into an efficacious therapeutic agent. The term "substituted", as used herein, means that one or more hydrogen on the designated atom is replaced with a selection from the indicated group, provided that the designated atom's normal valency is not exceeded, and that the substitution results in a stable compound. As used herein and in the claims, the term "amine protecting group" means any group known in the art of organic synthesis for the protection of amine groups. Such amine protecting groups include those listed in Greene, "Protective Groups in Organic Synthesis" John Wiley & Sons, New York (1981); and Geiger and Kδnig, "The Peptides: Analysis, Sythesis, Biology, Vol. 3, Academic Press, New York (1981), the disclosures of which are hereby incorporated by reference. Any amine protecting group known in the art can be used. . Examples of amine protecting groups include, but are not limited to, the following: 1) acyl types such as formyl, trifluoroacetyl, phthalyl, and p-toluenesulfonyl; 2) aromatic carbamate types such as benzyloxycarbonyl (Cbz) and substituted benzyloxycarbonyls, 1-(p-biphenyl)-1- methylethoxycarbonyl, and 9-fluorenylmethyloxycarbonyl (Fmoc) ; 3) aliphatic carbamate types such as tert- butyloxycarbonyl (Boc) , ethoxycarbonyl, diisopropylmethoxycarbonyl, and allyloxycarbonyl; 4) cyclic alkyl carbamate types such as cyclopent loxycarbony1 and adamantyloxycarbonyl; 5) alkyl types such as triphenylmethyl and benzyl; 6) trialkylsilane such as trimethylsilane; and 7) thiol containing types such as phenylthiocarbonyl and dithiasuccinoyl. As used herein and in the claims, "carboxylate protecting groups" means any group known in the art of organic synthesis for the protection of carboxylate groups. Such carboxylate protecting groups include S8 those listed in R. W. Roeske, in The Peptides, Vol 3; Protection of functional groups in peptide synthesis, (1981) , pp 1-99; Academic Press, the disclosures of which are hereby incorporated by reference. Any carboxylate protecting group known in the art can be • used. Examples of carboxylate protecting groups include, but are not limited to, the following: alkyl esters such as Cl to Cβ alkyl, C5 to Cβ cycloalkylalkyl and t-butyl; aryl esters such as benzyl, substituted benzyl, triphenylmethyl, diphenylmethyl, pentamethylbenzy1,tetramethylbenzy1, and trimethylbenzy1; or esters which can be cleaved by acidolysis, mild base treatment or mild reductive means such as trichloroethyl and phenacyl esters; other protecting groups can be CH2CH2CN, trialkylsilyl, phthalimidomethyl, anthrylmethyl, phenylfluorenyl, 4- picolyl and phenacyl. As used herein, "pharmaceutically acceptable salts and prodrugs" refer to derivatives of the disclosed compounds that are modified by making acid or base salts, or by modifying functional groups present in the compounds in such a way that the modifications are cleaved, either in routine manipulation or in vivo- to the parent compounds. Examples include, but are not limited to: mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; esters of carboxylates; acetate, formate and benzoate derivatives of alcohols and amines; and the like. Pharmaceutically acceptable salts of the compounds of the invention can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two; generally, nonaqueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. Lists of suitable salts are found in Remington's Pharmaffwi-.lnal Sciences. 17th ed.. Mack Publishing Company, Easton, PA, 1985, p. 1418, the disclosure of which is hereby incorporated by reference. The term "amino acid" as used herein means an organic compound containing both a basic amino group and an acidic carboxyl group. Included within this term are modified and unusual amino acids,such as those disclosed in, for example, Roberts and Vellaccio (1983) The Peptides f 5: 342-429, the teaching of which is hereby incorporated by reference. The term "amino acid residue" as used herein means that portion of an amino acid (as defined herein) that is present in a peptide or pseudopeptide. The term "peptide" as used herein means a linear compound that consists of two or more amino acids (as defined herein) that are linked by means of peptide or pseudopeptide bonds. Synthesis The following abbreviations are used herein: D-Abu D-2-aminobutyric acid β-Ala or bAla 3-aminopropionic acid Boc t-butyloxycarbonyl Boc-iodo-Mamb t-butyloxycarbonyl-3-aminomethyl-4-iodo- benzoic acid Boc-Mamb t-butyloxycarbonyl-3-aminomethylbenzoic acid Boc-ON [2-(tert-butyloxycarbonyloxylimino)-2- phenylacetonitrile BOP benzotriazole-1-yl-oxy-tris- (dimethylaminophosphonium- hexafluorophosphate) CO Cl2Bzl dichlorobenzyl CBZ Carbobenzyloxy DCC dicyclohexylcarbodiimide DIEA diisopropylethylamine di-NMeOrn N-αMe-N-γMe-ornithine DMAP 4-dimethylaminopyridine HBTU 2-(lH-Benzotriazol-1-yl)-1,1,3,3- tetramethyluronium hexafluorophosphate KHMDS potassium bis (trimethylsilyl)amide K-O-t-Bu potassium tert-butoxide LDA lithium isopropylamide LiHMDS lithium bis (trimethylsilyl)amide NaHMDS sodium bis (trimethylsilyl)amide Na-O-t-Bu sodium tert-butoxide NMeArg or MeArg α-N-methyl arginine NMeAmf N-Methylaminomethylphenylalanine NMeAsp α-N-methyl aspartic acid NMeGly or MeGly N-methyl glycine NMe-Mamb N-methyl-3-aminomethylbenzoic acid NMM N-methylmorpholine OcHex O-cyclohexyl OBzl O-benzyl PyBOP benzotriazole-1-yl-oxy-tris-(pyrolidino phosphonium hexafluorophosphate) PyBrOP Bromo-tris-pyrrolidino-phosphonium hexafluorophosphate TBTU 2-(lH-Benzotriazol-1-yl)-1,1,3,3- tetramethyluronium tetrafluoroborate Tos tosyl The following conventional three-letter amino acid abbreviations are used herein; the conventional one- letter amino acid abbreviations are not used herein: έl Ala = alanine Arg = arginine Asn = asparagine Asp = aspartic acid Cys = cysteine Gin = glutamine Glu = glutamic acid Gly = glycine His = histidine lie = isoleucine Leu = leucine Lys = lysine Met = methionine Nle = norleucine Orn = ornithine Phe = phenylalanine Phg = phenylglycine Pro = proline Ser = serine Thr = threonine Trp = tryptophan Tyr = tyrosine Val valine The present invention provides a process for the synthesis of compounds of formula (I) . The provided process is accomplished using inexpensive, simple starting materials and a more efficient approach to the problem of incorporating NMeArg into peptides. The overall process is novel: it utilizes novel reaction steps, novel reaction sequences, and novel reaction intermediates. In practicing the provided invention, knowledge of a number of standard techniques known to (cT those in the art is required. The following discussion and references are offered to provide such knowledge. Generally, peptides are elongated by deprotecting the α-amine of the C-terminal residue and coupling the next suitably protected amino acid through a peptide linkage using the methods described. This deprotection and coupling procedure is repeated until the desired sequence is obtained. This coupling can be performed with the constituent amino acids in a stepwise fashion, or condensation of fragments (two to several amino acids) , or combination of both processes, according to the methods described by Merrifield, J. Am . Chem . Soc , 85: 2149-2154 (1963); " The Peptides" , Vol. 1, 2, 3, 5, and 9, (1979-1987), E. Gross and J. Meienhofer, eds, Academic Press, , Academic Press, New York; Bodanszky, "Peptide Chemistry: A Practical Textbook" , Springer- Verlag, New York (1988); Bodanszky et al. " The Practice of Peptide Sythesiε" Springer-Verlag, New York (1984); the disclosures of which are hereby incorporated by reference. The coupling of two amino acid derivatives, an amino acid and a peptide, two peptide fragments, or the cyclization of a peptide can be carried out using standard coupling procedures such as the azide method, mixed carbonic acid anhydride (isobutyl chloroformate) method, carbodiimide (dicyclohexylcarbodiimide, diisopropylcarbodiimide, or water-soluble carbodiimides) method, active ester (p-nitrophenyl ester, N- hydroxysuccinic imido ester) method. Woodward reagent K method, carbonyldiimidazole method, phosphorus reagents such as BOP-C1, or oxidation-reduction method. Some of these methods (especially the carbodiimide) can be enhanced by the addition of 1-hydroxybenzotriazole. These coupling reactions may be performed in either solution (liquid phase) or solid phase. The functional groups of the constituent amino acids must be protected during the coupling reactions to avoid undesired bond formation. The protecting groups that can be used, methods of using them to protect amino acids, and methods to remove them are listed as above. The α-carboxyl group of the C-terminal residue is usually protected by an ester that can be cleaved to give the carboxylic acid. These protecting groups include but are not meant to be limited to: 1) alkyl esters such as methyl and t-butyl, 2) aryl esters such as benzyl and substituted benzyl, or 3) esters which can be cleaved by mild base treatment or mild, reductive means such as trichloroethyl and phenacyl esters. In the solid phase case, the C-terminal amino acid is attached to an insoluble carrier (usually polystyrene) . These insoluble carriers contain a group which will react with the carboxyl group to form a bond which is stable to the elongation conditions but readily cleaved later. Examples of which are: oxime resin (DeGrado and Kaiser (1980) J. Org. Chem . 45: 1295-1300) chloro or bromomethyl resin, hydroxymethyl resin, and aminomethyl resin. Many of these resins are commercially available with the desired C-terminal amino acid already incorporated. The α-amino group of each amino acid must be protected. Any amine protecting group known in the art can be used. Examples of these are: 1) acyl types such as formyl, trifluoroacetyl, phthalyl, and p- toluenesulfonyl; 2) aromatic carbamate types such as benzyloxycarbonyl (Cbz) and substituted benzyloxycarbonyls, 1- (p-biphenyl)-1- methylethoxycarbonyl, and 9-fluorenylmethyloxycarbonyl (Fmoc) ; 3) aliphatic carbamate types such as tert- butyloxycarbonyl (Boc) , ethoxycarbonyl, diisopropylmethoxycarbonyl, and allyloxycarbonyl; 4) cyclic alkyl carbamate types such as £>τ cyclopentyloxycarbonyl and adamantyloxycarbonyl; 5) alkyl types such as triphenylmethyl and benzyl; 6) trialkylsilane such as trimethylsilane; and 7) thiol containing types such as phenylthiocarbonyl and dithiasuccinoyl. The preferred α-amino protecting group is either Cbz, Boc or Fmoc. Many amino acid derivatives suitably protected for peptide synthesis are commercially available. The α-amino protecting group is cleaved prior to the coupling of the next amino acid. When the Cbz group is used, the reagents of choice are hydrogenation conditions using hydrogen at atmospheric pressure or in a Parr apparatus at elevated hydrogen pressure, or cyclohexene or ammonium formate over palladium, palladium hydroxide on charcoal or platinum oxide in methanol, ethanol or tetrahydrofuran, or combination of these solvents (P. N. Rylander, Hydrogenation Methods, Acedemic Press, 1985) . When the Boc group is used, the methods of choice are trifluoroacetic acid, neat or in dichloromethane, or HC1 in dioxane. The resulting ammonium salt is then neutralized either prior to the coupling or in situ with basic solutions such as aqueous buffers, or tertiary amines in dichloromethane or dimethylformamide. When the Fmoc group is used, the reagents of choice are piperidine or substituted piperidines in dimethylformamide, but any secondary amine or aqueous basic solutions can be used. The deprotection is carried out at a temperature between 0°C and room temperature. Any of the amino acids bearing side chain functionalities must be protected during the preparation of the peptide using any of the above-identified groups. Those skilled in the art will appreciate that the selection and use of appropriate protecting groups for these side chain functionalities will depend upon the amino acid and presence of other protecting groups in the peptide. The selection of such a protecting group is important in that it must not be removed during the deprotection and coupling of the α-amino group. For example, when Cbz is chosen for the α-amine protection the following protecting groups are acceptable: p- toluenesulfonyl (tosyl) moieties for arginine; t- butyloxycarbonyl, phthalyl, or tosyl for lysine or ornithine; alkyl esters such as cyclopentyl for glutamic and aspartic acids; alkyl ethers for serine and threonine; and the indole of tryptophan can either be left unprotected or protected with a formyl group. When Boc is chosen for the α-amine protection the following protecting groups are acceptable: p- toluenesulfonyl (tosyl) moieties and nitro for arginine; benzyloxycarbonyl, substituted benzyloxycarbonyls, or tosyl for lysine; benzyl or alkyl esters such as cyclopentyl for glutamic and aspartic acids; benzyl ethers for serine and threonine; benzyl ethers, substituted benzyl ethers or 2-bromobenzyloxycarbonyl for tyrosine; p-methylbenzy1, p-methoxybenzyl, acetamidomethyl, benzyl, or t-butylsulfonyl for cysteine; and the indole of tryptophan can either be left unprotected or protected with a formyl group. When Fmoc is chosen for the α-amine protection usually tert-butyl based protecting groups are acceptable. For instance, Boc can be used for lysine, tert-butyl ether for serine, threonine and tyrosine, and tert-butyl ester for glutamic and aspartic acids. Once the elongation and cyclization of the peptide is completed all of the protecting groups are removed. For the liquid phase synthesis the protecting groups are removed in the manner dictated by the choice of protecting groups. These procedures are well known to those skilled in the art. &c_. Unusual amino acids used in this invention can be synthesized by standard methods familiar to those skilled in the art ("The Peptides: Analysis, Sythesis, Biology, Vol. 5, pp. 342-449, Academic Press, New York (1981)). N-Alkyl amino acids can be prepared using proceedures described in previously (Cheung et al., (1977) Can . J. Chem. 55: 906; Freidinger et all, (1982) J. Org. Chem . 84: 77 (1982)), which are incorporated here by reference. The process of the present invention utilizes the general methods described above along with the novel methods described below to prepare the compounds of Formula (I) : Formula (I) A protected form of Gin is dehydrated to give the corresponding protected derivative of 2-amino-4-cyano- butyric acid, which then can be methylated exclusively at the 2-amino group. At a convenient point in the synthesis, the 4-cyano group is reduced to the corresponding aminomethyl group, giving a derivative of N α -methyl-ornithine. Guanylation of this amine, for instance as described in Z. Tian, R. W. Roeske, Int . Journal Pept . Prot . Res . 1991, 37: 425-429 and references therein, and which is hereby incorporated by reference, converts the N α -methyl-ornithine into a derivative of N α -MeArg. The process of the present invention begins with the sequence of steps shown in Scheme I. Scheme I PART A. PartA. Step 1 of the process begins with a commercially available compound (1) in which W is an amine protecting group, such as an alkyl-urethane, t-Boc, acyl, phthalyl, o-nitrophenylsulfenyl, Cbz, Fmoc, fluorenylphenyl, or some other amine protecting group as described above. The preferred protecting group is Cbz. The carboxamide group of formula (1) is dehydrated to the corresponding nitrile through the action of an appropriate dehydrating agent such as C0C12, acetic anhydride, or a coupling agent as described in the references: Z. Grzonka, B. Liberek, Bull. Acad. Pol . Sci . Ser. Sci . Biol . (1969), 17: 219-22; T. Yoneta, S. Shibahara, S. Fukatsu, S. Seki, Bull. Chem. Soc . Jpn . (1978); M. Wilchek, S. Ariely, A. Patchornik, J. Org. Chem . (1968), 33: 1258-9, which are hereby incorporated by reference. The preferred reagent is phosgene in toluene, THF, dioxane or methylene chloride or mixtures of these solvents at temperatures ranging from 0° to 50°C. The resulting aminonitrile compound (2) is then selectively alkylated at the α-amino group using an alkylating agent, such as an alkyl halide or dialkylsulfate, and a base, such as NaH or K-O-t-Bu, Na- O-t-Bu, LDA, LiHMDS, NaHMDS, or KHMDS, to introduce a Ci to C8 straight or branched alkyl group, or benzyl to produce compound (3) . The preferred method uses NaH or K-O-t-Bu as bases and alkyliodide or dialkylsulfate as the alkylating agent in THF or dioxane at temperatures ranging from 0° to 50° C. Alternatively, .compound (2) can be alkylated using the approach of Freidinger et al., J. Org. Chem . (1983), 48: 77-81. Par R PartB. In step 3, compound (3) is converted to the corresponding N-carboxyanhydride by reaction with an acid chloride, anhydride or a coupling agent as described in E. Frerot, J. Coste, J. Poncet, P. Jouin, B. Castro, Tetrahedron Lett . (1992), 33: 2815-2816. In the preferred method, this is accomplished using PCI5' in THF, dioxane, methylene chloride, or toluene between 0° and 50 °C. The resulting N-carboxyanhydride (4) is then reacted with an amino acid or an amino acid derivative in step 4. The amino acid can be used with, or without a carboxylate protecting group as described above. The preferred method of Step 4 for the preparation of the compound of formula (5) where Y is t-butyl is via reaction with Gly-t-butyl ester, in solvents such as DMF, methylene chloride, chloroform, acetontrile between -40° and 0 °C. Compound (5) can alternatively be prepared from compound (3) using steps 3a and 4a above. Compound (3) is coupled to an amino acid or an amino acid ester using well-known methods as described above giving rise to dipeptide (6) . Selective deprotection of the alpha- amino protecting group gives rise to compound (5) . Part C. R o SR Λ 5 o- v PartC. J ~ In step 5 (above) , the N α -alkyl dipeptide (5) is coupled with a α-amino-protected amino acid to give o tripeptide (7) using well-known methods for peptide coupling as previously described. The preferred method to prepare (7) wherein W is Boc, Y is t-butyl, and R 3 is alkyl, is to couple the Boc-protected amino acid to (5) using activating agents that include diphenylphosphinic chloride, chloroformates, TBTU, carbodiimides plus hydroxylamine derivatives. Bop, PyBOP, or PyBrOP as previously described at temperatures ranging from -30° to 70 °C in the presence of a tertiary amine such as DIEA in solvents including DMF or methylene chloride. ar P. NH 2 NC ( R 12 O W m R g O R 12 © < C ι H2 > " R 9 0 R 2 R 3 O R 5 ste 6 R 2 R 3 O R 5 I & 1Ω. Part D. Part D illustrates the method used to convert the substituted 2-amino-4-cyano-butyric acid moiety of (7 ) into the corresponding ornithine derivative in compound (8 ) , and into an Arg derivative in compound (10 ) . An advantage of the present invention is that this sequence of transformations can be carried out at any point that is convenient within the overall synthesis of a peptide. Step 6 involves the reduction of the nitrile to the corresponding aminomethyl function. This transformation can be carried out using reaction conditions well known in the literature for reducing cyano groups, as described in Tetrahedron Lett . , 4393 (1975); Modern Synthetic Reactions, H.O. House (1972); or Harting et al. J. Am . Chem . Soc , 50: 3370 (1928). The preferred method for preparing (8) from (7) involves reductive hydrogenation at elevated hydrogen pressure, with Ptθ2 in an alcohol solvent like ethanol between ambient temperature and about 60°C. Step 7 involves reaction of the amine (8) released in step 6 with a guanylating agent (9) in which XX is H or an amine protecting group as listed above and Z is a leaving group such as S03~, S-alkyl, O-alkyl. Methods for synthesizing guanidines are known in the art and described in " The Peptides" vol 2, 169-175; Garigipat et al, Tetrahedron Lett. 31: 1969 (1990); Kim et al. Tetrahedron Lett . 29: 3183 (1988); Miller and Bischoff, Synthesis 111, (1986) , Delle Monache, EPO Application #330629A2 (published 1989); and Bernard et al. Can . J. Chem . 36:1541 (1958) all of which are hereby incorporated by reference. In the preferred method XX is Cbz, and Z is S-ethyl or S-methyl, and this reagent is reacted with (8) in the presence of a tertiary amine such as DIEA in solvents such as water, methanol, ethanol, dioxane or combination of these solvents at ambient temperature to reflux temperature of the solvent. 7.)-. Part E . Jfl. 1 Part E. In Step 8 (above) , the free amino acid tripeptide (11) is prepared by the deprotection of compound (10) . For example, deprotection of (10) wherein Y is t-butyl alkyl and W is t-Boc may be accomplished using any of a variety of methods well known in the literature- for the deprotection of t-butyl esters and t-Boc groups. Such methods include: hydrogen chloride in dioxane; and trifluoroacetic acid neat or in methylene chloride. The preferred method, to prepare the free amino acid compound, (11) , by deprotection of compound (10) wherein W is t-Boc and Y is t-butyl alkyl, utilizes trifluoroacetic acid in methylene chloride or hydrogen chloride in dioxane, at ambient temperature. Part F. PartF. In Step 9, the fully elaborated protected linear peptide compound, (13) , is prepared by coupling the carboxylic acid compound, (12), and the amino tripeptide compound, (11) . This step may be carried out using any of the variety of methods well known in the literature for forming amide bonds, as previously described. The preferred coupling method for the preparation of the linear pentapeptide compound of formula (13) wherein G is t-Boc, involves preactivation of (12) to form an active ester using a carbodiimide and hydroxysuccinimide o or pentafluorophenol at 0 C to ambient temperature, followed by addition of (11) dissolved in- DMF or acetonitrile at 0° to 100 °C. In Step 10, the free amino acid pentapeptide compound, (14), is prepared by the deprotection of compound (13) . For example, deprotection of (14) wherein G is t-Boc may be accomplished using any of a variety of methods well known in the literature for the deprotection of t-butyl esters and t-Boc groups. Such methods include: hydrogen chloride in dioxane or ethyl acetate; and trifluoroacetic acid neat or in methylene chloride, chloroform, ether, or toluene. The preferred method to prepare the free amino acid compound (14) , is deprotection of compound (13) wherein G is t-Boc, utilizing trifluoroacetic acid in methylene chloride or hydrogen chloride in dioxane, at ambient temperature. In Step 11, the cyclic compound, (15) , is prepared by cyclization of the linear pentapeptide compound, (14) . This step may be accomplished using any of the variety of amide bond forming reactions well known in the literature as described above, or under conditions known to promote acrocyclization as described is R. Schmidt, K. Neubert, Int . Jour. Peptide . Prot . Res . (1991), 37: 502-507 which is hereby incorporated by reference. The preferred cyclization methods for the preparation of compounds of formula (15) from the linear compound, (14) , utilizes a tertiary amine as base, such as DIEA, and TBTU, BOP, PyBrOP, PyBOP, or a carbodiimide such as 1- (3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride or DCC in a solvent such as N,N- dimethylformamide or acetonitrile, at ambient temperature. In Step 12 a compound of formula (I), wherein R 4 is H, is formed: the β-carboxylic acid, (16), is prepared from the corresponding compound of formula (15) wherein R 6 is CH2C02Bn by catalytic hydrogenation: the protecting groups on the guanidino function are simultaneously removed if XX is Cbz or aaother protecting group which can be removed by hydrogenolysis. One may use any of the many hydrogenation methods well known in the literature, such as described in: P. N. Rylander, Hydrogenation Methods, Acedemic Press, (1985) . Such methods include: catalytic reduction with hydrogen over platinum oxide; catalytic reduction at elevated hydrogen pressure over palladium on charcoal; or phase transfer hydrogenation with cyclohexene or ammonium formate, in an appropriate solvent such as methanol or ethanol. The preferred method for the preparation of compound (7) wherein R 6 is CH2CO2Y and where Y is Cbz, involves hydrogenation of.compound (15) with 10% palladium on charcoal in an alcohol solvent, at a temperature between ambient temperature and 70° C. Alternatively, the reaction may be carried out with 10% palladium on charcoal, at elevated hydrogen pressure, in an alcohol solvent. Schema 2 15b 16a Scheme 2 Scheme 2 illustrates a process for the synthesis of Formula I wherein R 4 is other than H, e.g. an ester. The synthesis proceeds similarly to scheme 1, but differs at Part F where here the protecting groups on the α-amino group and the β-carboxylate are orthogonally removed. In the preferred method, G of (13) is Fmoc, and R 11 is CH2-C02-t-Bu. In the first reaction of Scheme 2, the Fmoc is removed using a secondary or tertiary amine, such as piperidine, in a polar organic solvent, such as DMF. Alternatively, this deblocking reaction step can be carried out in situ during the cyclization step if the cyclization reaction is carried out in the presence of DMAP or a similar base. Thus, in the prefered method, compound (13) wherein G is FMOC, is deprotected and cyclized by treating it with DMAP and TBTU in DMF. In the third reaction in Scheme 2, the carboxylate protecting group is removed. In the preferred method in which R6 is CH2-C02~t-Bu, the deprotection is effected using the conditions described above to convert compound (10) to (11) . The fourth reaction in Scheme 2 involves alkylation of the carboxylate that was liberated in the previous step. This is carried out using an alkyl halide or alkyl sulfonate ester, such as alkyl-tosylates, in DMF with a tertiary amine as base at temperatures ranging from 0 °C to 50 °C. Scheme 3 1L I≤. 18a Scheme3 The preparation of intermediate compound (12) is shown in Scheme 3. The pseudodipeptide (12) is prepared by coupling the amino carboxylic acid compound of formula (18) or formula (18A) , with the activated carboxylic acid of an appropriately substituted N-α protected amino acid of (19) wherein G is a protecting group such as Fmoc or t-Boc, using any of the amide bond forming reactions previously described. The preferred method for preparing the pseudodipeptide compound, (12) , wherein R is phenyl, is by reaction of the free amino acid compound, (18) wherein R 1 is phenyl, with a carboxylic acid, (19), activated with N,N'- carbonyldiimidazole, in the solvent N,N- dimethylformamide, at ambient temperature. Alternatively, the carboxylic acid can be activated as the N-hyroxysuccinate ester in a solvent such as methylene chloride or N,N-dimethylformamide. The amino carboxylic acid compound of formula (18) or formula (18A) can be purchased or can be prepared by reduction of the appropriately substituted cyano carboxylic acid compound (17) by methods well known in the literature for reducing cyano groups, as described in Tett . Lett . , 4393 (1975); Modern Synthetic Reactions, H.O. House (1972); or Harting et al. J. Am . Chem . Soc , 50: 3370 (1928) . The preferred method for preparing the amino acid (18) , wherein R* is phenyl from (17) involves reductive hydrogenation at elevated hydrogen pressure, with 10% palladium on charcoal in an alcohol solvent like ethanol between ambient temperature and 60°C. For example, reduction of 3- or 4-cyanobenzoic acid, which is a compound of formula (17) wherein R* is phenyl, under these conditions affords the corresponding benzyl amine of formula (18) . Other analogues of compounds of formula (18) and (18A) may be prepared by any of a number of methods well known in the literature or as described in the following Schemes. Scheme 4. 24- Scheme4 The N-alkylated compound of formula (24) can be prepared according to standard procedures, for example. Olsen, J. Org. Chem. (1970) 35: 1912) . This compound may also be prepared as shown in Scheme 4. Scheme.. 5-8 IA Scheme 5 (1) R ,5 L1 (IDHjO/HCl Scheme 6 2A fcv V Scheme 7 D i 5 (1) NHzOH.HCl/EtOH/Pyr. (it) P -C/Et0H/Hq O n./H2 Scheme 8 IA Schemes 5-8 show a number of alternative routes to intermediate compounds of formula (24) . Compound (24) falls within general formula (18) and is useful for the synthesis of compounds of formula (12) . Scheme 5 details a method for the preparation of compounds of formula (24) wherein R 15 is Cχ-C8 alkyl, Cχ-C8 cycloalkyl, or aryl. Scheme 8 shows a route for the preparation of compounds of formula (24) wherein R 1 ^ is alkyl or phenyl. Schemes 9 and 10 show routes for the preparation of compounds of formula (24) wherein R 1 ^ is CH3, or phenyl. Schema 3 Scheme 9 Alternative carbocylic residues for R 1 of the invention include aminoalkyl-naphthoic acid. Formula (29) , and aminoalkyl-tetrahydronaphthoic acid. Formula (30) as depicted above in scheme 9. Some other possible analogues for R 1 Formula (I) can be prepared according to a modification of standard procedures previously reported in the literature such as described in Earnest, I.,et al., Tett. Lett., (1990) 31: 4011-4014. An alternative process for the synthesis of compounds of Formula (I) is shown in Scheme 10 below. Scheme 10 Part A L Formula(V) An alternative process from scheme 1 is as follows and begins at compound (7) from scheme 1, part C above. The free amino acid tripeptide Formula (V) is prepared by the deprotection of compound (7) as in step 6 above. For example, deprotection of (7) wherein Y is benzyl and W is Cbz may be accomplished using any of a variety of methods well known in the literature for the deprotection of benzyl esters and Cbz groups. However, the reaction must be carefully monitored to avoid reduction of the nitrile. One may use any of the many hydrogentation methods well known in the literature, such as described in: P. N. Rylander, Hydrogenation Methods, Acedemic Press, (1985) . Such methods include: catalytic reduction with hydrogen over platinum oxide; catalytic reduction at elevated hydrogen pressure over palladium on charcoal; or phase transfer hydrogenation with cyclohexene or ammonium formate, in an appropriate solvent such as methanol or ethanol. The preferred method for the preparation of Formula (V) involves hydrogenation of compound (7) with 10% palladium on charcoal in an alcohol solvent, at a temperature between ambient temperature and 70° C. Alternatively, the reaction may be carried out with 10% palladium on charcoal, at elevated hydrogen pressure, in an alcohol solvent. © Part B. Formula (I) PartB. In Step 7, the fully elaborated protected linear peptide compound, (21), is prepared by coupling the carboxylic acid compound, (12), and the amino tripeptide compound, (20) . This step may be carried out using any of the variety of methods well known in the literature for forming amide bonds, as previously described. The preferred coupling method for the preparation of the linear pentapeptide compound of formula (21) wherein G is t-Boc, involves preactivation of (12) to form an active ester using a carbodiimide and hydroxysuccinimide or pentafluorophenol at 0 C to ambient temperature, ' followed by addition of (20) dissolved in'DMF or acetonitrile at 0° to 100 °C. In Step 8, the free amino acid pentapeptide compound, (22), is prepared by the deprotection of compound (21) . For example, deprotection of (21) wherein G is t-Boc may be accomplished using any of a variety of methods well known in the literature for the deprotection of t-Boc groups. Such methods include: hydrogen chloride in dioxane or ethyl acetate; and trifluoroacetic acid neat or in methylene chloride, chloroform, ether, or toluene. The preferred method to prepare the free amino acid compound (22) , is deprotection of compound (21) wherein G is t-Boc, utilizing trifluoroacetic acid in methylene chloride or hydrogen chloride in dioxane, at ambient temperature. In Step 9, the cyclic compound, (23) , is prepared by cyclization of the linear pentapeptide compound, (22) . This step may be accomplished using any of the variety of amide bond forming reactions well known in the literature as described above, or under conditions known to promote macrocyclization as described is R. Schmidt, K. Neubert, Int. Jour. Peptide . Prot . Res . (1991), 37: 502-507 which is hereby incorporated by reference. The preferred cyclization methods for the preparation of compounds of formula (23) from the linear compound, (22) , utilizes a tertiary amine as base, such as DIEA, and TBTU, BOP, PyBrOP, PyBOP, or a carbodiimide such as 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride or DCC in a solvent such as N,N- dimethylformamide or acetonitrile, at ambient temperature. In Step 10, the amino-β-carboxylic acid, (25), is prepared from the corresponding compound of formula (23) wherein R*> is CH2C02Bn by nitrile reduction using catalytic hydrogenation with simultaneous benzyl hydrogenolysis. This transformation can -be carried out using reaction conditions well known in the literature for reducing cyano groups, as described in Tett . Lett . , 4393 (1975); Modern Synthetic Reactions, H.O. House (1972); or Harting et al. J. Am . Chem. Soc , 50: 3370 (1928) . Step 11 involves reaction of the amine released in Step 10 with a guanylating agent (9) in which XX is H or an amine protecting group as listed above and Z is a leaving group such as SO3", S-alkyl, O-alkyl to form compounds of Formula (I) . Methods for synthesizing guanidines are given in The Peptides" vol 2, 169-175; Garigipat et al. Tetrahedron Lett . 31: 1969 (1990); Kim et al. Tetrahedron Lett . . 29: 3183 (1988); Miller and Bischoff, Synthesis 777, (1986), Delle Monache, EPO Application #330629A2 (published 1989); and Bernard et al. Can . J. Chem. 36:1541 (1958) all of which are hereby incorporated by reference. EXAMPLES All chemicals and solvents (reagent grade) were used as supplied from the vendors cited without further purification. t-Butyloxycarbonyl (Boc) amino acids and other starting amino acids may be obtained commercially from Bachem Inc., Bachem Biosciences Inc. (Philadelphia, PA) , Advanced ChemTech (Louisville, KY) , Peninsula Laboratories (Belmont, CA) , or Sigma (St. Louis, MO). 2- (lH-Benzotriazol-1-yl)-1,1,3, 3-tetramethyluronium hexafluorophosphate (HBTU) and TBTU were purchased from Advanced ChemTech. N-methylmorpholine (NMM) , /n-cresol, D-2-aminobutyric acid (Abu) , trimethylacetylchloride, diisopropylethylamine (DIEA) , 3-cyanobenzoic acid and [2-(tert-butyloxycarbonyloxylimino)-phenylacetonitrile] (Boc-ON) were purchased from Aldrich Chemical Company. Dimethylformamide (DMF) , ethyl acetate, chloroform (CHCI3) , methanol (MeOH) , pyridine and hydrochloric acid (HC1) were obtained from Baker. Acetonitrile, dichloromethane (DCM) , acetic acid (HOAc) , trifluoroacetic acid (TFA) , ethyl ether, triethylamine, acetone, and magnesium sulfate were purchased from EM Science. Palladium on carbon catalyst (10% Pd) was purchased from Aldrich Chemical Company or Fluka Chemical Company. Absolute ethanol was obtained from Quantum Chemical Corporation. Thin layer chromatography (TLC) was performed on Silica Gel 60 F254 TLC plates (layer thickness 0.2 mm) which were purchased from EM Separations. TLC visualization was accomplished using UV light, iodine, and/or ninhydrin spray. Melting points were determined using a Thomas Hoover or Electrothermal 9200 melting point apparatus and are uncorrected. NMR spectra were recorded on a 300 MHz General Electric QE-300, Varian 300, or Varian 400 spectrometer. Fast atom bombardment mass spectrometry (FAB-MS) was performed on a VG Zab-E double-focusing mass spectrometer using a Xenon FAB gun as the ion source or a Finnigan MAT 8230. The following examples represent (but are not intended to be limiting) the processes and intermediates of the present invention. m Example 1: Nfl-benzyloxvearbonvl-N g -methγl-4-cvano-I--2- min..butyric acid Z-Gln (28.03 g, 100 mmol) was dissolved in 300 mL THF in a flask bottle protectected from moisture and to it was added 100 mL 1.93 M phosgene in toluene (193 mmol) . The solution was stirred at room temperature for 2 h and concentrated at 30° C to 200 mL. Water (200 mL) was added slowly with stirring. After stirring at room temperature for 2 h, the organic phase was seperated, and the water phase was extracted with ethyl acetate twice. The combined organic solution was washed with brine four times, dried (MgSO_j) , and concentrated. The oily product was dried over KOH overnight. The dried oily product was taken up in 300 mL dry THF and 49.8 mL (800 mmol) methyl iodide in a flask bottle protected from moisture and the solution was cooled in an ice bath. To it was slowly added 10 g sodium hydride (250 mmol, 60% dispersion in oil) . The mixture was stirred in the ice bath for 1 h and then at room temperature for 22 h. Ethyl acetate (50 mL) was added, and after stirring for 10 min, 100 mL water was added slowly. The solution was acidified with a few drops of 4 N HCl to pH8-9 and then concentrated at 30° C to remove the organic solvents. Water (100 mL) was added followed by 10 mL 0.1 N sodium thiosulfate, and the solution was extracted with ether twice. The water layer was cooled in an ice bath and to it was slowly added 4 N HCl to pH 3 with stirring. The product , which crystallized during the acidification, was filtered, washed with water several times, and dried. Yield 26.0 g (94%). mp 81-83° C. iH-N R (CDC1 3 ) : δ=2.15 (m, IH) ; 2.38 (m, IH) ; 2.42 (m, 2H) ; 2.96 & 2.98 (2 s, cis & trans N- CH 3 ); 4.62 (m, IH) ; 4.90 (b, IH) ; 5.19 (s, 2H) ; 7.35 (m, 5H) . Example 2: Nfl-methvl-4-gyano-L-2-aminob.it.vric acid-N- carb_.κyanhydride To a solution of example 1 (11.05 g, 40 mmol) in .50 L dry THF cooled in an ice bath was added phosphorus pentachloride (15 g, 72 mmol) and the mixture was stirred for 2 h and concentrated to dryness. The residue was triturated with petroleum ether to give a solid which was filtered, washed with petroleum ether and dissolved in dry acetonitrile. Insoluble material was filtered off and the solution was concentrated. The solid was washed with cold ether and dried. Yield 5.86 g (87%). mp 90-92° C. !H-NMR (CDCI 3 ) : δ=2.18 (m, IH) ; 2.39 (m, IH); 2.60 (m, 2H) ; 3.02 (s, 3H) ; 4.28 (m, IH) . Example 3: N-Boe-D-2-aminobutyrγl-Nfl-ffiethyl-4-cvano-I.- 2-aminobutvrvl-olveine fc-hufrvl eater To a solution of glycine t-butyl ester hydrochloride (3.68 g, 22 mmol) in 40 mL chloroform and 4.84 mL N-methylmorpholine cooled to -40° C was added a solution of example 2 (3.36 g, 20 mmol) in 20 mL dry acetonitrile, the solution was stirred at -20° C for 1 h, and the solvent was reduced to about 10 mL. To a solution of N-Boc-D-2-aminobutyric acid dicyclohexylamine salt (8.08 g, 21 mmol) in 30 mL chloroform cooled to -10° C was added diphenylphosphinic chloride (3.91 mL, 20.5 mmol) and the mixture was stirred at -5° to -10° C for 1 h. To it was added the above prepared solution (10 mL) followed by 2.42 mL N- methylmorpholine. The mixture was stirred at 0° to -5° C for 24 h, and then concentrated. Ethyl acetate was added and insoluble material was filtered off. The filtrate was washed with NaHCθ 3 four times and with brine three times, dried over MgS0 4 , and concentrated to a small amount at which time the product crystallized. Petroleum ether was added, and after cooling, the solid was °i\ filtered, washed with petroleum ether, and dried. Yield 6.2 g (70%). mp 90-92° C. FAB-MS (MH + ) : Calculated 441.3; Found 441.3. Example 4: H-BQC-P-2--UBing__utγryl-P g -net-_γl-W^--- ffll -_ rbigbenzγloxyearbonγl.- -ar 7 invl- ? lveine -.-hutvl eater Example 3 (4.63 g, 10.5 mmol) was dissolved in 70 mL methanol in a Parr bottle and to it was added a cold solution of 1.2 mL concentrated hydrochloric acid (38%) in 10 mL methanol followed by 200 mg platinum(IV) oxide. The mixture was hydrogenated at 55 psi for 1 h, the catalyst was filtered off, and 2.09 mL (15 mmol) triethylamine was added. The solvent was removed under reduced pressure and the residue was taken up in 20 mL THF. To it was added N, N'-bisbenzyloxycarbonyl-S- methylisothiourea (3.58 g, 10 mmol) followed by 2.09 mL (15 mmol) triethylamine. The mixture was stirred overnight during which time the bottle was evacuated several times to remove the byproduct methanethiol. Ethyl acetate was added, and the solution was washed with 1% citric acid, brine, 5% NaHCθ 3 and brine, dried (MgS0_ι) , and concentrated. Crystallization from ethyl ether-petroleum ether gave 7.2 g (95%) product. FAB-MS (MH + ) : Calculated 755.4; Found 755.4. Example 5: p-2-aπι ngt>utγry_i-y fl -me hγl-W m . ^ }ϊ^- ■biaben-_γloxv__arbonvl.-L-aroinvl-ylveine TFA salt A solution of Example 4 (9 g, 11.9 mmol) in 90 mL 50% TFA in methylene chloride was stirred at room temperature for 2 h and the solution was concentrated at 30° C. Cold ether was added, and after standing, the solid was filtered, washed with ether, and dried. Yield 8.4 g (99%). FAB-MS (MH + ) : Calculated 599.3; Found 599.3. Example 6: N-Boc- -aspartvl fb_>nzvl.-3-(aminomethyli- benzoic acid 3-cyanobenzoic acid (3.38 g, 23 mmol) was dissolved in 30 mL THF by warming and stirring. Isopropanol (20 mL) was added and the solution was allowed to cool to room temperature. To it was added 2.5 mL precooled concentrated HCl (38%) followed by 160 mg platinum(IV) oxide. The mixture was hydrogenated at 55 psi overnight. The product precipitated during the hydrogenation. Ether (100 mL) was added and the mixture was stirred and then cooled. The precipitate was filtered, washed with cold ether, and dissolved in 40 ml DMF. The catalyst was filtered off and rinsed with DMF. BocAsp(Bzl)OSu (8.4 g, 20 mmol) was added followed by 7.7 mL (44 mmol) diisopropylethylamine. After stirring at room temperature for 5 h, the solution was added slowly to 200 mL 3% citric acid with stirring. After cooling, the precipitate was filtered, washed with water and cold ether, and dried. Yield 8.2 g (90%). mp 148-150° C. *H- NMR (DMSO-d δ ) : δ=1.38 (s, 9H) ; 2.62 (m, IH) ; 2.80 (m, IH) ; 4.32 (d, 2H) ; 4.40 (m, IH) ; 5.07 (s, 2H) ; 7.20 (d, IH) ; 7.36 (s, 5H) ; 7.44 (m, 2H) ; 7.81 (m, 2H) ; 8.46 (t, IH) ; 12.90 (s, IH) . Example 7: N-BPC-IrasPartYlfbfinZYl)~3_ (aminomefchvlϊhenzovl-P-g-aminobutvrvl-Nfl-methvl-Nffl. Nffll- fbi9benzγloxvcarbonv -I,-arginvl-σlvcine To a solution of example 6 (2.29 g, 5 mmol) and pentafluorophenol (1.01 g, 5.5 mmol) in 15 mL THF was added DCC (1.03 g, 5 mmol) and the mixture was stirred overnight. Dicyclohexylurea was filtered off and rinsed with THF, and the solvent was removed under reduced pressure. To the residue was added a solution of example 5 (3.56 g, 5 mmol) in 10 ml DMF followed by 2.1 mL (12 mmol) diisopropylethylamine. After stirring at room temperature for 6 h, 50 mL 5% citric acid was added followed by 80 mL ethyl acetate. The organic phase was seperated, washed with 1% citric acid and brine, dried (MgS0 4 ) , and concentrated. The residue was triturated with ether-petroleum ether to give 4.8 g (92%) product. FAB-MS (MH + ) : Calculated 1037.5; Found 1037.3. Example 8 : -aapartyl (benzyl) -3- (_u_ingmethyl) enzpy _■--___ 2-aminobutγrγl-i*I-π_e..hvl-N-i._ Nffl'-(biabenzvloxvearbonvl_ - 1,-artτinγl-ςrlγeine TFA aalfc A solution of example 7 (5.7 g, 5.5 mmol) in 50 mL 50% TFA in methylene chloride was stirred at room • temperature for 1 h and concentrated. The- residue was triturated with cold ether, and the solid was filtered, washed with ether, and dried. Yield 5.8 g (100%). FAB-MS (MH + ) : Calculated 937.4; Found 937.1. Example 9: Cvelor__-aaparfcγl(benzvli-3- (aminomethvl^ benzovl-g-2-aπιinobutvrγl-Nfl-me-ihvl-Nti- . Nffl'- (bi3benzvloxvearbonγH-I.-arginvl-plvevπ To a solution of TBTU (963 mg, 3 mmol) in 25 mL DMF was added slowly a solution of 3.15 g (3 mmol) example 8 in 25 mL DMF and 1 mL (9 mmol) N-methylmorpholine over a period of 1.5 h and stirring was continued for 2.5 h. The solution was added slowly to 200 mL 1% citric acid cooled in an ice bath and the precipitate was filtered, washed with water and ether, and dried. Yield 2.5 g (90%). FAB-MS (MH+) : Calculated 919.4; Found 919.0. Example 10: Cγelor__-aana_tγl-3- aminome_-hγl-benzoγl--->- 2-aminobt.frγrvl-Νfl-mefchvl-E-arqinvl-qlvcvl. A mixture containing example 9 (919 mg, 1 mmol), methanesulfonic acid (71 μL, 1.1 mmol) and 150 mg 10% palladium on carbon in 5 mL DMF was hydrogenated at atmospheric pressure for 4 h and the catalyst was filtered off and rinsed with DMF. The solution was added to 50 mL acetonitrile with stirring and the precipitate was filtered and washed with ether to give 590 mg (90%) methanesulfonic acid salt of the title compound which is over 90% pure. The product was dissolved in water and the pH of the solution was adjusted to pH 7.4 by addition of ammonium hydroxide. Acetone was added to give a precipitate. Crystallization from water gave pure zwitterion product. FAB-MS (MH + ) : Calculated 561.3; Found 561.3. Example 11: 3-(aminomefchγl.benzole acid hvdroehloride 3-cyanobenzoic acid (5.88 g, 40 mmol) was suspended in 50 mL THF and the mixture was warmed up with stirring. After all solid went into solution, 50 mL isopropanol was added and the solution was allowed to cool to room temperature. To it was added 4.2 mL precooled concentrated HCl followed by 300 mg platinum(IV) oxide. The mixture was hydrogenated at 55 psi overnight. Ether (50 mL) was added, and the precipitate was filtered, washed with ether and dissolved in methanol. The catalyst was filtered off and the solvent was removed under reduced pressure to give 6.2 g (82%) product. ! H-NMR (DMSO-d 6 ) : 5=4.08 (d, 2H) ; 7.53 (t, IH) ; 7.80 (d, IH) ; 7.94 (d, IH) ; 8.10 (s, IH) ; 8.65 (s, 3H) . Example 12: Fmoc-I,-a9Partγl(fc-butyH-3-faminnmethγlϊ- benzoie acid To a solution of FmocAsptBu OPfp (17.33 g, 30 mmol) and example 11 (6.19 g, 33 mmol) in 50 mL DMF cooled in an ice bath was added 11.5 mL (66 mmol) diisopropylethylamine, and after stirring at room temperature for 5 h, 200 mL 5% citric acid was added and the solution was extracted with ethyl acetate twice. The combined extracts were washed with brine, dried (MgSO_j) , and concentrated to give a solid which was washed with ether-petroleum ether and dried. Yield 16.3 g (100%). i H-NMR (DMSO-d 6 ) : δ=1.35 (s, 8H) ; 2.48 (dd, IH) ; 2.70 i (dd, IH) ; 4 . 2-4 . 4 (m, 6H) ; 7 . 30 (t , 2H) ; 7 . 4-7 . 5 (m, 4H) ; 7 .7-7 . 9 (m, 7H) ; 8 .55 (t , IH) ; 12 . 92 (s , IH) . Example 13 : Fmoe-__-aapartvl (fr-butyl l -3- (aminomethvl^benzovl-_--2-aminob-ityrvl-wa-methvl-Mfl-. Nttl- A mixture containing example 12 (10.89 g, 20 mmol), pentafluorophenol (4.05 g, 22 mmol) and DCC (4.13 g, 20 mmol) in 50 mL THF was stirred at room temperature overnight. Dicyclohexylurea was filtered off, rinsed with THF, and the filtrate was concentrated. To it was added a solution of example 5 (14.25 g, 20 mmol) in 40 mL DMF followed by 7.32 mL (42 mmol) diisopropylethylamine. The mixture was stirred at room temperature for 4 h, insoluble material was filtered off, and the filtrate was added to 200 mL 3% citric acid with stirring. The solution was extracted with ethyl acetate twice and the combined extracts were washed with brine, dried (MgSO_ι) , and concentrated. The residue was triturated with ether-petroleum ether to give 22 g (98%) product. FAB-MS (MH + ) : Calculated 1125.5; Found 1125.7. Example 14: CyclQT -aspartyl( ~butγl)~3- (aminomefchvl.benzovl-.D-2-aminobutvrvl-Nffl. Nffll- (biabenzvloxvcarbonvlϊ-I,-arσinvl-σlvcvn A solution of example 13 (22.5 g, 20 mmol) and 4- dimethylaminopyridine (14.66 g, 120 mmol) in 100 mL DMF was stirred overnight at room temperature and added slowly to a solution of TBTU (6.42 g, 20 mmol) in 200 mL DMF over 3 h and stirring was continued for 1 h. Ethyl acetate (1000 mL) was added and the solution was washed with 1% citric acid 2 times, brine 3 times and concentrated to dryness. The residue was taken up in THF and after filtration, the solvent was removed under reduced pressure to give a solid which was washed with ether and dried . Yield 16 g ( 90% ) . FAB-MS (MH + ) : Calculated 885 . 4 ; Found 885 .2 . Example 15 : 2-aτninobutyrvl-Wfl-. WflH- (biabenzvloxvearbonγl . -X,-ar P invl- qlycyll A solution of example 14 (16 g, 18 mmol) in 200 mL 50% TFA in methylene chloride was stirred at room temperature for 1.5 h and then concentrated. The residue was triturated with ether to give 14.5 g (97%) product. FAB-MS (MH + ) : Calculated 829.4; Found 829.1. Example 16 : Cycle . -aspartyl (acetQ__γπιethyl) -3- (aminomethγllbenzoγl-g-2-aminobutvrvl-I,-arqinγl-olγevl. A mixture containing example 15 (1.42 g, 1.7 mmol), bromomethyl acetate (980 mL, 10 mmol) and triethylamine (976 mL, 7 mmol) in 10 mL DMF was stirred at room temperature overnight. Ethyl acetate was added and the solution was washed with brine 3 times, dried (MgSO_ι) , concentrated, and dried. The residue was taken up in 8 mL DMF and to it was added 130 mL (2 mmol) methanesulfonic acid followed by 150 mg 10% palladium on carbon. The mixture was hydrogenated at atmospheric pressure for 2 h, the catalyst was filtered off, and the solution was diluted with water. Purification using se ipreparative HPLC gave 650 mg (51) pure product. FAB- MS (MH + ) : Calculated 633.3; Found 633.2. Example 17: Cyelor_.-aapar_.vl(pivalovloxvmethvl.-3- (aminomethyl)benzovl-_-)-2-aminobutvrvl---aroinvl-olvπy11 A mixture containing example 15 (4.14 g, 5 mmol), chloromethyl pivalate (4.3 mL, 30 mmol), triethylamine (2.8 mL, 20 mmol), Nal (4.5 g, 30 mmol) in 10 mL DMF was stirred at room temperature for 18 h. Ethyl acetate (100 mL) was added and the solution was washed with brine 3 times, dried (MgS0 4 ) , and concentrated. The residue was taken up in 15 L ethyl acetate and passed through a silica gel column using ethyl acetate-THF (1:1) as eluent to give 1.5 g pure product. The product was dissolved in 10 mL DMF and hydrogenated at atmospheric pressure using 10% palladium on carbon (130 mg) in the presence of methanesulfonic acid (100 mL) for 2 h. The catalyst was filtered off, rinsed with DMF, and the solution was diluted with water. Purification using semipreparative HPLC gave 1 g (26%) pure product. FAB-MS (MH + ) : Calculated 675.3; Found 675.3. Example 18: Cvclori_-aapartγl-(iaopropvloxvcarbonvl- oxvmefchvl 3-aminomethvlibenzovl-g-2-aminobufcyrvl-. - arginyl-qlycyll A mixture containing example 15 (4.14 g, 5 mmol), chloromethyl isopropyl carbonate (4.58 g, 30 mmol), triethylamine (2.8 mL, 20 mmol), Nal (4.5 g, 30 mmol) in 10 mL DMF at stirred at room temperature for 18 h. Ethyl acetate (100 mL) was added and the solution was washed with brine 3 times, dried (MgSθ ) , and concentrated. The residue was taken up in 10 mL ethyl acetate-THF (1:1) and passed through a silica column using ethyl acetate- THF (1:1) as eluent to give 1.6 g product. The product was dissolved in 10 mL DMF and hydrogenated at atmospheric pressure using 10% palladium on carbon (150 mg) in the presence of 130 mL for 2 h. The catalyst was filtered off, rinsed with DMF, and the solution was diluted with water. Purification using semipreparative HPLC gave lg (25%) pure product. FAB-MS (MH + ) : Calculated 667.3; Found 667.3.

Claims: S6 CLAIMS WHAT IS CLAIMED IS : 1. A process for the preparation of compounds of formula I : Formula (I) comprising the steps of : (a) alkylating the α-amino group of an aminonitrile of the formula : OH to produce a compound of the formula (IV) : Formula(IV) and coupling with amino acid derivatives to produce a nitrile tripeptide of the formula: (b) reducing the nitrile group from the product of step (a) to form the formula: NH- / 2 (c) reacting the amino group of the product of step (b) with a guanylating agent of the formula: , to produce the formula : (d) deprotecting the carboxyl and α-amino groups of the product from step (c) to form the compound of the formula: loo and coupling the above formula with a carboxylic acid derivative of formula: to produce a protected linear peptide of formula: (e) removing the protecting group (G) of the product of Step (d) to produce a deprotected linear peptide of formula (III) : Formula (III) (f) cyclizing the deprotected linear peptide of Formula (III ) to produce a cyclic peptide of formula (II) : Formula (II) (g) then converting the Formula (II ) by a series of deprotecting and/or alkylating steps to a compound of formula (I ) : loz. Formula (I) wherein : W erein : p and p ' are 0 or 1 ; R 19 is a C 6 -C 14 saturated, partially saturated, or aromatic carbocyclic ring system or heterocyclic ring system composed of carbon atoms and at least 1- 3 heteroatoms selected from N, 0, S; all these ring systems may be optionally substituted with 0-2 R 7 ; R 17 and R 16 are independently selected from the group: hydrogen, C 1 -C 4 alkyl, optionally substituted with halogen, C 1 -C 2 alkoxy, and |o3 benzyl; R15 a nd R18 are independently selected from the group: 5 hydrogen, C1-C8 alkyl substituted with 0-2 R 8 , C2-C8 alkenyl substituted with 0-2 R 8 , C2-C8 alkynyl substituted with 0-2 R 8 , 10 C3-C8 cycloalkyl substituted with 0-2 R 8 , C6-C10 bicycloalkyl substituted with 0-2 R 8 , 15 aryl substituted with 0-2 R 13 , and a heterocylic ring system composed of 5- 10 atoms including 1-3 nitrogen, oxygen, or sulfur heteroatoms with the remaining 20 atoms being carbon, optionally substituted with 0-2 R 13 ; R 15 and R 17 can alternatively join to form a 5-7 membered carbocyclic ring 25 substituted with 0-2 R 13 ; R 18 and R 16 can alternatively join to form a 5-7 membered carbocyclic ring substituted with 0-2 R 13 ; 30 R 7 is independently selected at each occurrence from the group: phenyl, benzyl, phenethyl, phenoxy, 35 benzyloxy, halogen, hydroxy, nitro, cyano, C1-C5 alkyl, C3-C6 cycloalkyl. ι©4- C3-C6 cycloalkylmethyl, C7-C10 arylalkyl, C1-C4 alkoxy, -CO2R 20 / sulfonamide, formyl, C 3 -C 6 cycloalkoxy, -OC(=0)R 20 , -C(=0)R 20 ,-OC(=0)OR 20a , 5 -OR 20 , -CH 2 OR 20 , and C 1 -C 4 alkyl optionally substituted with -NR20R21. R 8 is independently selected at each occurrence from the group: 10 =0, F, Cl, Br, I, -CF 3 , -CN, -C02R 20 , -C(=0)NR 2 θR 21 , _ C H 2θR 20 / -OC(=0)R20, -CH 2 NR 20 R 21 , and -NR 20 R 21 ; 15 R 13 is independently selected at each occurrence from the group: phenyl, benzyl, phenethyl, phenoxy, benzyloxy, halogen, hydroxy, nitro, 20 cyano, C1-C5 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkylmethyl, C7-C10 arylalkyl, C1-C4 alkoxy, -CO2R 20 , sulfonamide, formyl, C 3 -C 6 cycloalkoxy, -OC(=0)R 20 , -C(=0)R 20 ,-OC(=0)OR 20a , 25 -OR 20 , -CH 2 OR 20 , and C 1 -C 4 alkyl optionally substituted with -NR 20 R 21 ; R 20 is independently selected at each occurrence from the group: 30 H, Ci-Cβ alkyl, aryl, - (C1-C6 alkyl)aryl, and C3-C6 alkoxyalkyl; R 20a i S R 20, t> ut not H; R 21 is independently selected at each 35 occurrence from the group: H, C1-C4 alkyl, and benzyl; R 12 is H or C1-C8 alkyl; R 2 is H, Ci-Cβ alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkylmethyl, C1-C6 cycloalkylethyl, phenyl, phenylmethyl, CH2OH, CH2SH, CH2OCH3, CH2SCH3, CH2CH2SCH3, (CH 2 ) S NH 2 , (CH 2 ) S NHC(=NH) (NH 2 ), or (CH 2 ) S NHR 21 , wherein s is 3-5; or R 12 and R 2 can be taken together to -form -(CH2) t ~ / or -CH2SC(CH3)2~ , wherein t is 2-4; R 3 is H or Ci-Cβ alkyl or C1-C4 alkylphenyl; R 9 is H, C1-C8 alkyl; R 5 is H, C1-C8 alkyl; R 11 is H or Ci-Cβ alkyl; R 4 is selected independently at each occurrence from: H, Ci-Cβ alkyl; C 2 -C 8 alkenyl; C 2 -C 8 alkynyl; C 3 -C 8 cycloalkyl; Ci-Cβ alkyl substituted with (i) aryl, optionally substituted with 1-2 substituents independently selected from halogen, phenyl, C 3 .-C 5 alkyl, C 1 -C 5 alkoxy, N0 2 , -S(0) 0 - 2 (C 1 -C 5 alkyl), OH, N (R 22 ) 2 , CO 2 R 22 , CON (R 22 ) or -C V F W where v = 1 to 3 and w = 1 to (2v+l ) ; ( ii ) C3-C8 cycloalkyl ; (iϋ) aryl, optionally substituted with 1-2 substituents independently selected from halogen, phenyl, C 1 -C5 alkyl, C 1 -C5 alkoxy, NO2, -S (0) 0-2 (C1-C5 alkyl), OH, N(R 22 ) 2 , CO2R 22 , CON(R 22 )2 or -C V F W where v = 1 to 3 and w = 1 to (2v+l); C2-C8 alkyl, alkenyl or alkynyl; substituted with 1-2 substituents independently selected from C 1 -C 4 alkyl, C3-C8 cycloalkyl, C 1 -C5 alkoxy, phenoxy, benzyloxy, halogen, NO2 CN, CO2R 22 , CON(R 2 ) , N(R 24 )COR 24 , morpholino, 2-(l- morpholino) ethoxy, N(R 22 ) , N + (R 22 ) 3 , 0C0CH3, -CH(R 24 )OR 26 ; -CH(R )OC(=0)R 25 ; -CH(R 24 )OC(=0)OR 26 ; -CH (R 24 ) OC (=0)N (R 25 ) 2; -CH (R 24 )N (R 24 ) C (=0)R 24 ; -CH(R 24 )C0 2 R 25 ; -CH(R 24 )C0N(R 22 ) 2 ; -CH(R 24 )N(R 2 ) 2 ; 27 \oη ; wherein R 22 is selected independently from: H, Cι-Cχo alkyl, C3-C10 cycloalkyl, C4-C12 alkylcycloalkyl, aryl, -(C1-C10 alkyl)aryl, or C3-C10 alkoxyalkyl; when two R 22 groups are bonded to a single N, said R 22 groups may alternatively be taken together to form -(CH 2 )2-5~ oτ -(CH 2 )0(CH 2 )-; R 24 is selected independently from: H, Ci-Cβ alkyl, C 3 -C 10 cycloalkyl, phenyl, or benzyl; R 25 is selected from: H; \ 0β Ci-Ce alkyl or C 3 -C 8 cycloalkyl, said alkyl or cycloalkyl being substituted with 1-2 groups independently selected from: 5 (i) C 1 -C 4 alkyl; (ii) C 3 -C 8 cycloalkyl; (iii) C 1 -C 5 alkoxy; (iv) aryl substituted with 0-2 groups independently selected from: 10 halogen, phenyl, Ci-Cβ alkyl, C1-C6 alkoxy, NO 2 -S (C 1 -C 5 alkyl), -SO(Cι-C 5 alkyl), -SO 2 (C 1 -C 5 alkyl), -OH, -N(R 22 ) 2 , -CO2R 22 , or -C V F W where v = 1 15 to 3 and w = 1 to (2v+l) ; aryl substituted with 0-2 groups independently selected from: halogen, phenyl, Ci-Cg alkyl, C 1 -C 6 alkoxy, N0 , -S(Cι-C 5 alkyl; . -SO(Cι-C 5 20 alkyl), -S0 2 (C 1 -C 5 alkyl), -OH, -C V F W where v = 1 to 3 and w = 1 to (2v+l); 25 R 26 is selected from: Ci-Cβ alkyl or C 3 -C 8 cycloalkyl, said alkyl or cycloalkyl being substituted with 1-2 groups independently selected from: 30 (i) C 1 -C 4 alkyl; (ii) C 3 -C 8 cycloalkyl; (iii) C 1 -C 5 alkoxy; (iv) aryl substituted with 0-2 groups independently selected from: 35 halogen, phenyl, C1-C6 alkyl, C-.-C6 \o°l alkoxy, NO 2 , -S(C 1 -C 5 alkyl), -SO(Cι-C 5 alkyl), -S0 2 (C 1 -C 5 alkyl), -OH, -N(R 2 ) 2 , -C0 2 R 22 , -C(=0)N(R 22 ) , or -C V F W where v = 1 5 to 3 and w = 1 to (2v+l); aryl substituted with 0-2 groups independently selected from: halogen, phenyl, Ci-Ce alkyl, Ci-Cβ alkoxy, NO 2 , -S(Cι-C 5 alkyl), -SO(C 1 -C 5 10 alkyl), -S0 2 (C 1 -C 5 alkyl), -OH, -C V F„ where v = 1 to 3 and w = 1 to (2v+l); 15 R 27 is selected from: H; Ci-Ce alkyl or C 3 ~Cβ cycloalkyl, said alkyl or cycloalkyl being substituted with 1-2 groups independently selected 20 from: (i) Ci-Ce alkyl; (ii) C 1 -C6 alkoxy; (iii) aryl substituted with 0-2 groups independently selected from: 25 halogen, phenyl, Ci-Cβ alkyl, Ci-Cε alkoxy, NO 2 , -S (C 1 -C 5 alkyl), -SO(Cι-C 5 alkyl), -S0 2 (C 1 -C 5 alkyl), -OH, -N(R 22 ) 2 , -C0 2 R 22 , -C(=0)N(R 2 ) 2 , or -C V F W where v = 1 30 to 3 and w = 1 to (2v+l); aryl substituted with 0-2 groups independently selected from: halogen, phenyl, C 1 -C6 alkyl, Ci-Cβ alkoxy, N0 , -S(Cι-C 5 alkyl), -SO(Cι-C 5 35 alkyl), -S0 (C 1 -C 5 alkyl), -OH, -N(R 22 ) 2 , -C0 R 22 , -C(=0)N(R 22 ) 2 , or Wo -C V F W where v = l to 3 and w = 1 to (2v+l); R 28 is selected from: H, C 1 -C 5 alkyl, or benzyl; R 6 is CH2CO2Ϊ; n is 1 to 4; m is 0 to 3; W and G are H or amine protecting groups and are independently selected from the group consisting of: acyl types such as formyl, trifluoroacetyl, phthalyl, and p- toluenesulfonyl; aromatic carbamate types such as benzyloxycarbonyl (Cbz) and substituted benzyloxycarbonyls, 1-(p- biphenyl)-1-methylethoxycarbonyl, and 9- fluorenylmethyloxycarbonyl (Fmoc) ; aliphatic carbamate types such as tert-butyloxycarbonyl (Boc) , ethoxycarbonyl, diisopropylmethoxycarbonyl, and allyloxycarbonyl; cyclic alkyl carbamate types such as cyclopentyloxycarbonyl and adamantyloxycarbony1; alkyl types such as triphenylmethyl and benzyl; trialkylsilane such as trimethylsilane; and thiol containing types such as phenylthiocarbonyl and dithiasuccinoylalkyl-urethane; sulfenyl types such as O-nitrophenylsulfenyl (NPS) and 0- nitropyridylsulfenyl (NPYS) ; Y is H or a suitable carboxylate protecting group and can be selected from the group consisting of: alkyl esters such as Ci to C8 alkyl, C5 to C8 cycloalkylalkyl and t- butyl; aryl esters such as benzyl, substituted benzyl, triphenylmethyl, 5 diphenylmethyl, pentamethylbenzy1,tetramethylbenzy1, and trimethylbenzyl; or esters which can be cleaved by acidolysis, mild base treatment or mild reductive means such as 10 trichloroethyl and phenacyl esters; other protecting groups can be CH2CH2CN, trialkylsilyl, phthalimidomethyl, anthrylmethyl, phenylfluorenyl, 4-picolyl and phenacyl; 15 XX is H or a suitable amine protecting group and is selected from the group consisting of: acyl types such as formyl, trifluoroacetyl, phthalyl, and p-toluenesulfonyl; aromatic 20 carbamate types such as benzyloxycarbonyl (Cbz) and substituted benzyloxycarbonyls, 1- (p-biphenyl)-1-methylethoxycarbonyl, and 9- fluorenylmethyloxycarbonyl (Fmoc) ; aliphatic carbamate types such as tert-butyloxycarbonyl 25 (Boc) , ethoxycarbonyl, diisopropylmethoxycarbonyl, and allyloxycarbonyl; cyclic alkyl carbamate types such as cyclopentyloxycarbonyl and adamantyloxycarbonyl; alkyl types such as 30 triphenylmethyl and benzyl; trialkylsilane such as trimethylsilane; and thiol containing types such as phenylthiocarbonyl and dithiasuccinoylalkyl-urethane; sulfenyl types such as O-nitrophenylsulfenyl (NPS) , 35 nitropyridylsulfenyl (NPYS), 2,3, 6-trimethyl- 4-methoxybenzenesulfonamide (Mtr-NR2) , 2,4,6- W . trimethoxybenzenesulfonamide (Mtb-NR2) , 2,6- dimethy1-4-methoxybenzenesulfonamide (Mds- NR2) / pentamethylbenzenesulfonamide (Pme-NR2) , 2,3,5,6-tetramethyl-4-methoxybenzene- sulfonamide (Mte-NR2) , 4-methoxybenzene- sulfonamide (Mbs-NR2) 2,4,6- trimethylbenzenesulfonamide (Mts-NR2) , 2,6- dimethoxy-4-methoxybenzenesulfonamide (iMds- NR2) and 2,2,5,7,8-Pentamethylchroman-6- sulfonamide (Pmc-NR2) ; and Z is a leaving group such as Sθ3~, S-alkyl, 0- alkyl or an O-substituted derivative of hydroxylamine. A process of claim 1 wherein: n is 3; .19 is selected from: R 15 and R 18 are independently selected from H, C1-C4 alkyl, phenyl. benzyl, phenyl-(C2-C4)alkyl, C 1 -C 4 alkoxy; R 17 and R 16 are independently H or C 1 -C 4 alkyl; R 7 is H, Ci-Cβ alkyl, phenyl, halogen, or C 1 -C 4 alkoxy; R 11 is H or C 1 -C 3 alkyl; R 12 is H or CH3; R 3 is H, Ci-Cβ alkyl; R 9 is H, C 1 -C 3 alkyl; R 5 is H, C 1 -C 3 alkyl; R^ is selected independently from: H, Ci-Cβ alkyl; C 2 -C 8 alkenyl; C 2 -C 8 alkynyl; C 3 -C 8 cycloalkyl; Ci-Cβ alkyl substituted with (i) aryl, optionally substituted with 1-2 substituents independently selected from halogen, phenyl, C 1 -C 5 alkyl, C 1 -C 5 alkoxy, N0 , -S(0) 0 - 2 (C 1 -C 5 alkyl), OH, N(R 22 ) 2 / CO2R 22 / CON(R 22 )2 or -C V F W where v = 1 to 3 and w = 1 to (2v+l) ; (ii) C 3 -C 8 cycloalkyl; (iii) aryl, optionally substituted with 1-2 substituents independently selected from halogen, phenyl, C 1 -C 5 alkyl, C 1 -C 5 alkoxy, NO 2 , -S(0) 0 - 2 (C 1 -C 5 alkyl), OH, N(R 2 ) 2 , C0 2 R 22 , CON(R 22 ) 2 or -C V F„ where v = 1 to 3 and w = 1 to (2v+l); C 2 -C 8 alkyl, alkenyl or alkynyl; substituted with 1-2 substituents independently selected from C 1 -C 4 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 5 alkoxy, phenoxy, benzyloxy, halogen, Nθ 2/ CN, CO 2 R 22 , CON(R 22 ) 2 , N(R 24 )COR 24 , morpholino, 2-(l- morpholino)ethoxy, N(R 22 ) 2/ N + (R 22 ) 3 , 0C0CH3, CF 3 , S(O) 0 -2R 22a ; -CH(R 24 )OR 26 ; -CH(R 24 )OC(=0)R 25 ; -CH(R 2 )OC(=0)OR 26 ; -CH(R 24 )OC(=0)N(R 25 ) 2 ; -CH(R 24 )C02R 25 ; process of claim 1 wherein: U S ' R 2 is H or C 1 -C 4 alkyl; R 5 , R 9 , Rl6. R17 a nd R18 are H; R 11 and R 12 are H or CH3; R 15 is H, C1-C4 alkyl, phenyl, benzyl, or phenyl-(C2-C4)alkyl; and R 3 is H or C 1 -C 3 alkyl; R 4 is selected independently from: H, -CH(R 24 )OC(=0)R 25 ; -CH(R 4 )OC(=0)OR 26 ; -CH 2 OC(=0)N(R 25 ) 2 ; -CH 2 CH 2 N(R 22 ) 2 ; -CH(R 24 )C0 R 25 ; ; wherein R 24 is selected independently from: H, Ci-Ce alkyl, phenyl, or benzyl; and R 27 is selected from: C 1 -C 5 alkyl, benzyl or phenyl. 4. A process of claim 1 wherein: n is 3; \\ > p is 0, p' is 1; R 19 is phenyl R 5 , R 9 , R 11 , and R 12 are H; R 2 is ethyl; R 3 is methyl; and R 4 is selected from: H; -CH(R 24 )OC(=0)R 25 ; -CH(R 24 )OC(=0)OR 26 ; ; wherein R 24 is C 1 -C 4 linear alkyl or H; and R 27 is C 1 -C 4 alkyl, benzyl, or phenyl. 5. A process for the preparation of compounds of formula I : in Formula (I) , comprising the steps of: (a) alkylating an aminonitrile of the formula: ς OH to produce a compound of the formula (IV) : Formula(IV) converting formula (IV) above through a series of deprotecting steps and coupling with amino acid derivatives to produce a protected nitrile tripeptide of the formula (V) : . Formula (V) (b) coupling formula (V) with a carboxylic acid derivative of the formula: wherein G is a suitable amine protecting group, to produce a protected linear peptide of formula: (c) removing the protecting groups of the product of Step (b) to produce a deprotected linear peptide of formula : (d) cyclizing the deprotected linear peptide of the product of step (c) to produce a cyclic peptide of formula (VI) : H Formula (VI) (e) reducing the nitrile from the product of step (d) to form the formula: l 2 θ HH . H (f) reacting the product of step (e) with a guanylating agent of the formula: , leading directly to a compound of Formula I, or via a series of deprotecting and/or alkylating steps converting to a compound of formula (I) : Formula (I) wherein : R 1 is wh erein: p and p' are 0 or 1; 5 R 19 is a Cg-Ci saturated, partially saturated, or aromatic carbocyclic ring system or heterocyclic ring system composed of carbon atoms and at least 1- 3 heteroatoms selected from N, 0, S; all 10 these ring systems may be Optionally substituted with 0-2 R 7 ; R 17 and R 16 are independently selected from the group: 15 hydrogen, C 1 -C 4 alkyl, optionally substituted with halogen, C 1 -C 2 alkoxy, and 20 benzyl; R 1 ^ and R 18 are independently selected from the group: 25 hydrogen, Ci-Cβ alkyl substituted with 0-2 R 8 , C2-C8 alkenyl substituted with 0-2 R 8 , C2-C8 alkynyl substituted with 0-2 R 8 , C3-C8 cycloalkyl substituted with 0-2 30 R 8 , C6-C10 bicycloalkyl substituted with 0-2 R 8 , \ X2. aryl substituted with 0-2 R 13 , and a heterocylic ring system composed of 5- 10 atoms including 1-3 nitrogen, oxygen, 5 or sulfur heteroatoms with the remaining atoms being carbon, optionally substituted with 0-2 R 13 ; R 15 and R 17 can alternatively join to form a 10 5-7 membered carbocyclic ring substituted with 0-2 R 13 ; R 18 and R 16 can alternatively join to form a 5-7 membered carbocyclic ring 15 substituted with 0-2 R 13 ; R 7 is independently selected at each occurrence from the group: 20 phenyl, benzyl, phenethyl, phenoxy, benzyloxy, halogen, hydroxy, nitro, cyano, C1-C5 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkylmethyl, C7-C10 arylalkyl, C1-C4 alkoxy, -CO2R 20 , 25 sulfonamide, formyl, C 3 -C 6 cycloalkoxy, -OC(=0)R 20 , -C(=0)R 20 ,-OC(=0)OR 20a , -OR 20 , -CH 2 OR 20 , and C 1 -C 4 alkyl optionally substituted with -NR 20 R 21 ; 30 R 8 is independently selected at each occurrence from the group: =0, F, Cl, Br, I, -CF 3 , -CN, -CO2R 20 , -C(=O)NR 20 R 21 , -CH 2 OR 20 , -OC(=O)R20, 35 -CH 2 NR 20 R 21 , and -NR 20 R 21 ; R 13 is independently selected at each occurrence from the group: phenyl, benzyl, phenethyl, phenoxy, benzyloxy, halogen, hydroxy, nitro, cyano, C1-C5 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkylmethyl, C7-C10 arylalkyl, C1-C4 alkoxy, -CO2R 20 / sulfonamide, formyl, C 3 -C 6 cycloalkoxy, -OC(=0)R 20 , -C(=0)R 20 ,-OC(=0)OR 20a , -OR 20 , -CH 2 OR 20 , and C 1 -C 4 alkyl optionally substituted with -NR 20 R 21 ; R 20 is independently selected at each occurrence from the group: H, C1-C8 alkyl, aryl, -(C1-C6 alkyl)aryl, and C3-C6 alkoxyalkyl; R 20a s R 20, but n ot H; R 21 is independently selected at each occurrence from the group: H, C1-C4 alkyl, and benzyl; R 12 is H or C1-C8 alkyl; R 2 is H, Ci-Cβ alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkylmethyl, C1-C6 cycloalkylethyl, phenyl, phenylmethyl, CH2OH, CH2SH, CH2OCH3, CH2SCH3, CH2CH2SCH3, (CH 2 ) S NH 2 , (CH 2 ) S NHC(=NH) (NH 2 ) , or (CH 2 ) S NHR 21 , wherein s is 3-5; or R 12 and R 2 can be taken together to form -(CH2)t" / or -CH 2 SC(CH 3 ) 2 - , wherein t is 2-4; l H R 3 is H or Ci-Cβ alkyl or C1-C4 alkylphenyl; R 9 is H, C1-C8 alkyl; R 5 is H, C1-C8 alkyl; R 11 is H or Ci-Ce alkyl; R4 is independently selected at each occurrence from: H, Cι-C 8 alkyl; C 2 -C 8 alkenyl; C 2 -C 8 alkynyl; C 3 -C 8 cycloalkyl; Ci-Cβ alkyl substituted with (i) aryl, optionally substituted with 1-2 substituents independently selected from halogen, phenyl, C 1 -C 5 alkyl, C 3 .-C 5 alkoxy, NO 2 , -S(0) 0 - 2 (C 1 -C 5 alkyl), OH, N(R 2 )2, CO2R 22 , CON(R 22 ) 2 or -C V F W where v = 1 to 3 and w = 1 to (2v+l) ; (ii) C 3 -C 8 cycloalkyl; (iii) aryl, optionally substituted with 1-2 substituents independently selected from halogen, phenyl, C 1 -C 5 alkyl, C 1 -C5 alkoxy, NO 2 , -S(0)0- 2 (C1-C5 alkyl), OH, N(R 22 )2, C0 2 R 22 , CON(R 2 ) or -C V F„ where v = 1 to 3 and w = 1 to (2v+l); 12.5 C2-C8 alkyl, alkenyl or alkynyl; substituted with 1-2 substituents independently selected from C1-C4 alkyl, C3-C8 cycloalkyl, C3.-C5 alkoxy, phenoxy, benzyloxy, halogen, NO2, CN, CO2R 22 , CON(R 22 ) , N(R 24 )COR 24 , morpholino, 2-(l- morpholino) ethoxy, N(R 22 ) 2 , N + (R 22 ) 3 , 0C0CH3, CF 3 , S(0)o-2R 22 / -CH(R 24 )OR 26 ; -CH(R 24 )OC(=0)R 25 ; -CH(R 24 )OC(=0)OR 26 ; -CH (R 24 ) OC (=0)N (R 25 ) 2; -CH(R 24 )N(R 24 )C(=0)R 24 ; -CH(R 2 )C02R 25 ; -CH(R 2 )CON(R 22 ) 2 ; -CH(R 2 )N(R 2 ) ; wherein 5 R 22 is selected independently from: H, Ci-Cio alkyl, C3-C10 cycloalkyl, C4-C12 alkylcycloalkyl, aryl, -(C1-C10 alkyl)aryl, or C3-C10 alkoxyalkyl; 10 when two R 22 groups are bonded to a single N, said R 22 groups may alternatively be taken together to form -(CH2)2-5~ or -(CH 2 )0(CH 2 )-; 15 R 24 is selected independently from: H, Ci-Ce alkyl, C 3 -C 10 cycloalkyl, phenyl, or benzyl; R 25 is selected from: 20 H; Ci-Cβ alkyl or C 3 -C 8 cycloalkyl, said alkyl or cycloalkyl being substituted with 1-2 groups independently selected from: 25 (i) C1-C4 alkyl; (ii) C 3 -C 8 cycloalkyl; (iii) C 1 -C 5 alkoxy; (iv) aryl substituted with 0-2 groups independently selected from: \7-l halogen, phenyl, Ci-Cβ alkyl, C -Cβ alkoxy, NO 2 , -S (C 1 -C 5 alkyl), -SO(Cι-C 5 alkyl), -S0 (C 1 -C 5 alkyl), -OH, -N(R 22 ) 2 , -C0 2 R 22 , 5 -C(=0)N(R 2 ) 2 , or -C V F W where v = 1 to 3 and w = 1 to (2v+l); aryl substituted with 0-2 groups independently selected from: halogen, phenyl, Ci-Cε alkyl, Ci-Cβ alkoxy, 10 NO 2 , -S(Cι-C 5 alkyl), -SO(Cι-C 5 alkyl), -SO 2 (C 1 -C 5 alkyl), -OH, -N(R 22 ) , -C0 2 R 22 , -C(=0 ' )N(R 22 )2, ©r -C V F W where v = 1 to 3 and w = 1 to (2v+l); 15 R 26 is selected from: Ci-Cβ alkyl or C 3 -C 8 cycloalkyl, said alkyl or cycloalkyl being substituted with 1-2 groups independently selected 20 from: (i) C 1 -C 4 alkyl; (ii) C 3 -C 8 cycloalkyl; (iii) C 1 -C 5 alkoxy; (iv) aryl substituted with 0-2 groups 25 independently selected from: halogen, phenyl, Ci-Cε alkyl, C 1 -C6 alkoxy, 0 2 -S(C 1 -C 5 alkyl), -SO(Cι-C 5 alkyl), -S0 2 (C 1 -C 5 alkyl), -OH, -N(R 22 ) 2 , -C0 2 R 22 , 30 -C(=0)N(R 22 )2, or -C V F„ where v = 1 to 3 and w = 1 to (2v+l); aryl substituted with 0-2 groups independently selected from: halogen, phenyl, C3.-C6 alkyl, C1-C6 alkoxy, 35 N0 , -S(Cι-C 5 alkyl), -SO(C 1 -C 5 alkyl), -S0 2 (C 1 -C 5 alkyl), -OH, 1 -2-Φ -N(R 22 ) 2 , -C0 2 R 22 , -C(=0)N(R 22 ) 2 , or -C V F W where v = 1 to 3 and w = 1 to (2v+l); R 27 is selected from: H Ci-Cβ alkyl or C3-C 8 cycloalkyl, said alkyl or cycloalkyl being substituted with 1-2 groups independently selected from: (i) Cι-C 6 alkyl; (ii) Ci-Ce alkoxy; (iii) aryl substituted with 0-2 groups independently selected from: halogen, phenyl, C_-C 6 alkyl, C 1 -C 6 alkoxy, NO 2 , -S (C 1 -C 5 alkyl), -SO(Cι-C 5 alkyl), -S0 2 (C 1 -C 5 alkyl) , -OH, -N(R 22 ) 2 , -C0 2 R 22 , -C(=0)N(R 22 )2, or -C V F W where v = 1 to 3 and w = 1 to (2v+l); aryl substituted with 0-2 groups independently selected from: halogen, phenyl, C 1 -C 6 alkyl, Ci-Cβ alkoxy, N0 2 , -S(Cι-C 5 alkyl), -SO(Cι-C 5 alkyl), -S0 2 (C 1 -C 5 alkyl), -OH, -N(R 22 ) 2 , -C0 2 R 22 , -C(=0)N(R 22 ) 2 , or -C V F„ where v = 1 to 3 and w = 1 to (2v+l); R 28 is selected from: H, C 1 -C 5 alkyl, or benzyl; R 6 is CH2CO2Y; n is 1 to 4; m is 0 to 3 ; W and G are H or amine protecting groups and are independently selected from the group consisting of: acyl types such as formyl, trifluoroacetyl, phthalyl, and p- toluenesulfonyl; aromatic carbamate types such as benzyloxycarbonyl (Cbz) and substituted benzyloxycarbonyls, 1-(p- biphenyl)-1-methylethoxycarbonyl, and 9- fluorenylmethyloxycarbonyl (Fmoc) ; aliphatic carbamate types such as tert-butyloxycarbonyl (Boc) , ethoxycarbonyl, diisopropylmethoxycarbonyl, and allyloxycarbonyl; cyclic alkyl carbamate types such as cyclopentyloxycarbonyl and adamantyloxycarbony1; alkyl types such as triphenylmethyl and benzyl; trialkylsilane such as trimethylsilane; and thiol containing types such as phenylthiocarbonyl and dithiasuccinoylalkyl-urethane; sulfenyl types such as O-nitrophenylsulfenyl (NPS) and 0- nitropyridylsulfenyl (NPYS) ; Y is H or a suitable carboxylate protecting group and can be selected from the group consisting of: alkyl esters such as Ci to C8 alkyl, C5 to C8 cycloalkylalkyl and t- butyl; aryl esters such as benzyl, substituted benzyl, triphenylmethyl, diphenylmethy1, pentamethylbenzy1,tetramethylbenzy1, and trimethylbenzyl; or esters which can be cleaved by acidolysis, mild base treatment or mild rε uctive means such as trichloroethyl and phenacyl esters; other 13D protecting groups can be CH2CH2CN, trialkylsilyl, phthalimidomethyl, anthrylmethyl, phenylfluorenyl, 4-picolyl and phenacyl; 5 XX is H or a suitable amine protecting group and is selected from the group consisting of: acyl types such as formyl, trifluoroacetyl, phthalyl, and p-toluenesulfonyl; aromatic 10 carbamate types such as benzyloxycarbonyl (Cbz) and substituted benzyloxycarbonyls, 1- (p-biphenyl)-1-methylethoxycarb ' onyl, and 9- fluorenylmethyloxycarbonyl (Fmoc) ; aliphatic carbamate types such as tert-butyloxycarbonyl 15 (Boc) , ethoxycarbonyl, diisopropylmethoxycarbonyl, and allyloxycarbonyl; cyclic alkyl carbamate types such as cyclopentyloxycarbonyl and adamantyloxycarbonyl; alkyl types such as 20 triphenylmethyl and benzyl; trialkylsilane such as trimethylsilane; and thiol containing types such as phenylthiocarbonyl and dithiasuccinoylalkyl-urethane; sulfenyl types such as O-nitrophenylsulfenyl (NPS) , 25 nitropyridylsulfenyl (NPYS), 2,3, 6-trimethyl- 4-methoxybenzenesulfonamide (Mtr-NR2), 2,4,6- trimethoxybenzenesulfonamide (Mtb-NR2) , 2,6- dimethy1-4-methoxybenzenesulfonamide (Mds- NR2) , pentamethylbenzenesulfonamide (Pme-NR2) , 30 2,3,5, 6-tetramethyl-4-methoxybenzene- sulfonamide (Mte-NR2), 4-methoxybenzene- sulfonamide (Mbs-NR2) , 2,4,6- trimethylbenzenesulfonamide (Mts-NR2) , 2,6- dimethoxy-4-methoxybenzenesulfonamide (iMds- 35 NR2), and 2,2,5,7, 8-Pentamethylchroman-6- sulfonamide (Pmc-NR2) ; and 13, Z is a leaving group such as SO3A S-alkyl, 0- alkyl or an O-substituted derivative of hydroxylamine. A process of claim 5 wherein: n is 3; R 19 is selected from: R 15 and R 18 are independently selected from H, C1-C4 alkyl, phenyl, benzyl, phenyl-(C2-C4) alkyl, C 1 -C 4 alkoxy; R 17 and R 16 are independently H or C 1 -C 4 alkyl; R 7 is H, Ci-Cβ alkyl, phenyl, halogen, or C 1 -C 4 alkoxy; R 11 is H or C1-C3 alkyl; R 12 is H or CH3; R 3 is H, C1-C8 alkyl; R 9 is H, C1-C3 alkyl; R 5 is H, C1-C3 alkyl; R 4 is selected independently from: H, Ci-Cβ alkyl; C2-C8 alkenyl; C2-C8 alkynyl; C3-C8 cycloalkyl; Ci-Ce alkyl substituted with (i) aryl, optionally substituted with 1-2 substituents independently selected from halogen, phenyl, C1-C5 alkyl, C1-C5 alkoxy, N0 2 , -S (0) 0-2 -C1-C5 alkyl), OH, N(R 22 )2. CO2R 22 , CON(R 2 ) 2 or -C V F„ where v = 1 to 3 and w = 1 to (2v+l) ; (ii) C3-C8 cycloalkyl; (iii) aryl, optionally substituted with 1-2 substituents independently selected from halogen, phenyl, C1-C5 alkyl, C1-C5 alkoxy, NO2, -S (0) 0-2 (C1-C5 alkyl), OH, N(R 22 ) 2/ C0 2 R 22 , CON(R 2 ) or -C V F where v = 1 to 3 and w = 1 to (2v+l) ; C2-C8 alkyl, alkenyl or alkynyl; substituted with 1-2 substituents independently selected from C 1 -C 4 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 5 alkoxy, phenoxy, benzyloxy, halogen, NO 2 , CN, CO 2 R 22 , CON(R 22 )2/ N(R 24 )COR 24 , morpholino, 2-(l- morpholino)ethoxy, N(R 22 )2, N + (R 22 ) 3 , OCOCH3, CF 3 , S(O) 0 -2R 22 ; -CH(R 24 )OR 26 ; -CH(R 2 )OC(=0)R 25 ; -CH(R 24 )OC(=0)OR 26 ; -CH(R 2 )OC(=0)N(R 25 ) 2 ; -CH(R 24 )C0 R 25 ; 7. A process of claim 5 wherein: R 2 is H or C 1 -C 4 alkyl; R 5 , R 9 , R 16 , R 17 and R 18 are H; R 11 and R 12 are H or CH3; R 15 is H, C1-C4 alkyl, phenyl, benzyl, or phenyl-(C2-C4)alkyl; and R 3 is H or C 1 -C 3 alkyl; \ i- R 4 is selected independently from: H, -CH(R 24 )OC(=0)R 25 ; -CH(R 24 )OC(=0)OR 26 ; -CH 2 OC(=0)N(R 25 ) 2 ; -CH2CH 2 N(R 2 ) 2 ; -CH(R 24 )C0 2 R 25 ; R 24 is selected independently from: H, C_-Cβ alkyl, phenyl, or benzyl; R 27 is selected from: C 1 -C 5 alkyl, benzyl or phenyl. 8. A process of claim 5 wherein: n is 3; p is 0, p' is 1; R 19 is phenyl R 5 , R 9 , R 11 , and R 12 are H; R 2 is ethyl; R 3 is methyl; and I35 " R 4 is selected independently from: H; -CH(R 24 )OC(=0)R 25 ; -CH(R 24 )OC(=0)OR 26 ; R 24 is C1-C4 linear alkyl or H; R 27 is C1-C4 alkyl, benzyl, or phenyl 9. A process for the preparation of an intermediate compound of the formula (II) : . NXX \ NH / H Formula (II) comprising the steps of cyclizing a compound of formula (III) : | fr Formula (III) wherein : n is 1 to 4 ; R 1 where in : p and p 1 are 0 or 1 ; R 9 is a C 6 _ Ci saturated, partially saturated, or aromatic carbocyclic ring system or heterocyclic ring system composed of carbon atoms and at least 1- 3 heteroatoms selected from N, 0, S; all these ring systems may be optionally substituted with 0-2 R 7 ; R 17 and R 16 are independently selected from the group: hydrogen, C 1 -C 4 alkyl, optionally substituted with halogen, C1-C 2 alkoxy, and benzyl; 5 R 1 ^ and R 18 are independently selected from the group: hydrogen, 10 C1-C8 alkyl substituted with 0-2 R 8 , C2-C8 alkenyl substituted with 0-2 R 8 , C2-C8 alkynyl substituted with 0-2 R 8 , C3-C8 cycloalkyl substituted with 0-2 R 8 , 15 C6-C10 bicycloalkyl substituted with 0-2 R 8 . aryl substituted with 0-2 R 13 , and 20 a heterocylic ring system composed of 5- 10 atoms including 1-3 nitrogen, oxygen, or sulfur heteroatoms with the remaining atoms being carbon, optionally substituted with 0-2 R 13 ; 25 R 15 and R 17 can alternatively join to form a 5-7 membered carbocyclic ring substituted with 0-2 R 13 ; 30 R 18 and R 16 can alternatively join to form a 5-7 membered carbocyclic ring substituted with 0-2 R 13 ; R 7 is independently selected at each 35 occurrence from the group: 136 phenyl, benzyl, phenethyl, phenoxy, benzyloxy, halogen, hydroxy, nitro, cyano, C1-C5 alkyl, C3-C6 cycloalkyl, 5 C3-C6 cycloalkylmethyl, C7-C10 arylalkyl, C1-C4 alkoxy, -CO2R 20 , sulfonamide, formyl, C 3 -C 6 cycloalkoxy, -OC(=0)R 20 , -C(=0)R 20 ,-OC(=0)OR 20a , -OR 20 , -CH 2 OR 20 , and C 1 -C 4 alkyl 10 optionally substituted with -NR 20 R 21 ; R 8 is independently selected at each occurrence from the group: 15 =0, F, Cl, Br, I, -CF 3 , -CN, -Cθ2R 20 / -C(=O)NR 20 R 21 , -CH 2 OR 20 , -OC(=O)R20, -CH NR 20 R 21 , and -NR 0 R 21 ; R 3 is independently selected at each 20 occurrence from the group: phenyl, benzyl, phenethyl, phenoxy, benzyloxy, halogen, hydroxy, nitro, cyano, C1-C5 alkyl, C3-C6 cycloalkyl, 25 C3-C6 cycloalkylmethyl, C7-C10 arylalkyl, C1-C4 alkoxy, -CO2R 20 / sulfonamide, formyl, C 3 -C 6 cycloalkoxy, -0C(=0)R 20 , -C(=0)R 20 ,-OC(=0)OR 20a , -OR 20 , -CH 2 OR 20 , and C 1 -C 4 alkyl 30 optionally substituted with -NR 20 R 21 ; R 20 is independently selected at each occurrence from the group: H, Ci-Cβ alkyl, aryl, -(Ci-Ce 35 alkyl) aryl, and C3-C6 alkoxyalkyl; R 20 a is R 20 ' but not H; I3η R 21 is independently selected at each occurrence from the group: H, C1-C4 alkyl, and benzyl; R 12 is H or C1-C8 alkyl; R 2 is H, Ci-Cβ alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkylmethyl, C1-C6 cycloalkylethyl, phenyl, phenylmethyl, CH2OH, CH2SH, CH2OCH3, CH2SCH3, CH2CH2SCH3, (CH2) S NH 2 , (CH 2 ) S NHC(=NH) (NH 2 ) , or (CH ) S NHR 21 , wherein s is 3-5; or R 12 and R 2 can be taken together to form -(CH2) t ~ , or -CH2SC(CH3)2~ , wherein t is 2-4; R 3 is H or Ci-Cβ alkyl; R 9 is H, C1-C8 alkyl; R 5 is H, C1-C8 alkyl; R 11 is H or Cι-C 8 alkyl; R6 is CH2CO2Y; Y is a suitable carboxylate protecting group and can be selected from the group consisting of: alkyl esters such as Ci to Cδ alkyl, C5 to Cβ cycloalkylalkyl and t- butyl; aryl esters such as benzyl, substituted benzyl, triphenylmethyl, diphenylmethyl, pentamethylbenzyl,tetramethylbenzy1 , and i io trimethylbenzyl; or esters which can be cleaved by acidolysis, mild base treatment or mild reductive means such as trichloroethyl and phenacyl esters; other 5 protecting groups can be CH2CH2CN, trialkylsilyl, phthalimidomethyl, anthrylmethyl, phenylfluorenyl, 4-picolyl and phenacyl; and 10 XX is H or a suitable amine protecting group and is selected from the group consisting of: acyl types such as formyl, trifluoroacetyl, phthalyl, and p-toluenesulfonyl; aromatic carbamate types such as benzyloxycarbonyl 15 (Cbz) and substituted benzyloxycarbonyls, 1- (p-biphenyl)-1-methylethoxycarbonyl, and 9- fluorenylmethyloxycarbonyl (Fmoc) ; aliphatic carbamate types such as tert-butyloxycarbonyl (Boc) , ethoxycarbonyl, 20 diisopropylmethoxycarbonyl, and allyloxycarbonyl; cyclic alkyl carbamate types such as cyclopentyloxycarbonyl and adamantyloxycarbony1; alkyl types such as triphenylmethyl and benzyl; trialkylsilane 25 such as trimethylsilane; and thiol containing types such as phenylthiocarbonyl and dithiasuccinoylalkyl-urethane; sulfenyl types such as O-nitrophenylsulfenyl (NPS) , nitropyridylsulfenyl (NPYS), 2,3, 6-trimethyl- 30 4-methoxybenzenesulfonamide (Mtr-NR2) , 2,4,6- trimethoxybenzenesulfonamide (Mtb-NR2) / 2,6- dimethyl-4-methoxybenzenesulfonamide (Mds- NR2) , pentamethylbenzenesulfonamide (Pme-NR2) , 2,3,5, 6-tetramethyl-4-methoxybenzene- 35 sulfonamide (Mte-NR2), 4-methoxybenzene- sulfonamide (Mbs-NR2) , 2,4,6- IHi trimethylbenzenesulfonamide (Mts-NR2)/ 2,6- dimethoxy-4-methoxybenzenesulfonamide (iMds- NR2), and 2,2,5,7, 8-Pentamethylchroman-6- sulfonamide (Pmc-NR2) . 10. A process of claim 9 wherein: n is 3; R! 9 is selected from: R 15 and R 18 are independently selected from H, C1-C4 alkyl, phenyl, benzyl, phenyl- (C2-C4)alkyl, C 3 .-C 4 alkoxy; R 17 and R 16 are independently H or C 1 -C 4 alkyl; R 7 is H, Ci-Cβ alkyl, phenyl, halogen, or C 1 -C 4 alkoxy; R 11 is H or C 1 -C 3 alkyl; R 12 is H or CH3 ; R 9 is H, C 1 -C 3 alkyl; R 5 is H, C 1 -C 3 alkyl; and XX is selected from the group consisting of: t-Boc, acyl, phthalyl, o- nitrophenylsulfenyl, Cbz, Fmoc, and fluorenylphenyl. 11. A process of claim 9 wherein: R 2 is H or C1-C4 alkyl; R 5 , R 9 , R 16 , R 17 and R 18 are H; R 11 , and R 12 are H or CH3; or R 2 and R 12 together are -(CH2)3- R 15 is H, C1-C4 alkyl, phenyl, benzyl, or phenyl- (C2-C4)alkyl; and R 3 is H or C 1 -C 3 alkyl. 12. A process of claim 9 wherein: p is 0, p' is 1; n is 3; R 19 is phenyl; R 5 , R 9 , R 11 , and R 12 are H; 1+3 R 2 is ethyl; R 3 is methyl; R 6 is CH2~OBn, CH2-OtBu, or CH2~0-tBoc; and XX is Cbz or Boc. 13. A process for the preparation of an intermediate compound of formula (IV) : Formula (IV) comprising the steps of: (a) dehydrating the carboxamide group of the formula: H ' N >=o to the corresponding nitrile to produce the formula: Nς OH 1H-+ (b) then selectively alkylating the product of step (a) at the α-amino group using a suitable alkylating agent to produce formula (IV) above, wherein: R 3 is H or CI-CΘ alkyl; m is 0 to 3; and W is a suitable amine protecting group and is selected from the group consisting of: acyl types such as formyl, trifluoroacetyl, phthalyl, and p- toluenesulfonyl; aromatic carbamate types such as benzyloxycarbonyl (Cbz) and substituted benzyloxycarbonyls, 1-(p-biphenyl)-1- methylethoxycarbonyl, and 9- fluorenylmethyloxycarbonyl (Fmoc) ; aliphatic carbamate types such as tert-butyloxycarbonyl (Boc) , ethoxycarbonyl, diisopropylmethoxycarbonyl, and allyloxycarbonyl; cyclic alkyl carbamate types such as cyclopentyloxycarbonyl and adamantyloxycarbonyl; alkyl types such as triphenylmethyl and benzyl; trialkylsilane such as trimethylsilane; and thiol containing types such as phenylthiocarbonyl and dithiasuccinoylalkyl- urethane. 14. An intermediate compound selected from the formulae II, III, IV, V and VI: Formula (II) Formula (III) Formula (IV) / Formula (V) f 3.110. CN / H Formula (VI) iM-k wherein: R 1 p and p' are 0 or 1; R 19 is a C 6 ~Ci 4 saturated, partially saturated, or aromatic carbocyclic ring system or heterocyclic ring system composed of carbon atoms and at least 1- 3 heteroatoms selected from N, 0, S; all these ring systems may be optionally substituted with 0-2 R 7 ; R 17 and R 16 are independently selected from the group: hydrogen, C 3. -C 4 alkyl, optionally substituted with halogen, C 1 -C 2 alkoxy, and benzyl; R 1 ^ and R 18 are independently selected from the group: hydrogen, Ci-Cβ alkyl substituted with 0-2 R 8 , C2-C8 alkenyl substituted with 0-2 R 8 , C2-C8 alkynyl substituted with 0-2 R 8 , C3-C8 cycloalkyl substituted with 0-2 R 8 , C6-C10 bicycloalkyl substituted with 0-2 R 8 , aryl substituted with 0-2 R 13 , and 5 a heterocylic ring system composed of 5- 10 atoms including 1-3 nitrogen, oxygen, or sulfur heteroatoms with the remaining atoms being carbon, optionally 10 substituted with 0-2 R 13 ; R 15 and R 17 can alternatively join to form a 5-7 membered carbocyclic ring substituted with 0-2 R 13 ; 15 R 18 and R 16 can alternatively join to form a 5-7 membered carbocyclic ring substituted with 0-2 R 13 ; 20 R 7 is independently selected at each occurrence from the group: phenyl, benzyl, phenethyl, phenoxy, benzyloxy, halogen, hydroxy, nitro, 25 cyano, C1-C5 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkylmethyl, C7-C10 arylalkyl, C1-C4 alkoxy, -CO2R 20 , sulfonamide, formyl, C 3 -C 6 cycloalkoxy, -OC(=0)R 20 , -C(=0)R 20 ,-OC(=0)OR 20a , 30 -OR 20 , -CH 2 OR 20 , and C 1 -C 4 alkyl optionally substituted with -NR 20 R 21 ; R 8 is independently selected at each occurrence from the group: 35 ι -8 =0, F, Cl, Br, I, -CF 3 , -CN, -C02R 20 / -C(=O)NR 20 R 21 , -CH 2 OR 20 , -OC(=O)R20, -CH 2 NR 20 R 21 , and -NR 20 R 21 ; R 13 is independently selected at each occurrence from the group: phenyl, benzyl, phenethyl, phenoxy, benzyloxy, halogen, hydroxy, nitro, cyano, C1-C5 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkylmethyl, C7-C10 arylalkyl, C1-C4 alkoxy, -CO2R 20 / sulfonamide, formyl, C 3 -C 6 cycloalkoxy, -OC(=0)R 20 , -C(=0)R 20 ,-OC(=0)OR 20a , -OR 20 , -CH 2 OR 20 , and C 1 -C 4 alkyl optionally substituted with -NR 20 R 21 ; R 20 is independently selected at each occurrence from the group: H, Ci-Cβ alkyl, aryl, - (C1-C6 alkyl)aryl, and C3-C6 alkoxyalkyl; R 20a s R 20, b ut not H ; R 21 is independently selected at each occurrence from the group: H, C1-C4 alkyl, and benzyl; R 12 is H or C1-C8 alkyl; R 2 is H, Ci-Cβ alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkylmethyl, C1-C6 cycloalkylethyl, phenyl, phenylmethyl, CH2OH, CH2SH, CH2OCH3, CH2SCH3, CH2CH2SCH3, (CH ) s NH 2 , (CH 2 ) S NHC(=NH) (NH 2 ) , or (CH ) S NHR 21 , wherein s is 3-5; or R^ 2 and R 2 can be taken together to form -(CH2) t ~ / or -CH 2 SC(CH3) 2 ~ , wherein t is 2-4; R 3 is H or Ci-Cβ alkyl; R 9 is H, C1-C8 alkyl; R 5 is H, C1-C8 alkyl; R 11 is H or Ci-Cβ alkyl; R 6 is CH2CO2Y or CH2CO2R 4 ; R 4 is independently selected at each occurrence from: H, Ci-Cβ alkyl; C 2 -C 8 alkenyl; C 2 -C 8 alkynyl; C 3 -C 8 cycloalkyl; Ci-Ce alkyl substituted with (i) aryl, optionally substituted with 1-2 substituents independently selected from halogen, phenyl, C 1 -C 5 alkyl, C 1 -C 5 alkoxy, N0 2 , -S (0) 0 - 2 (C 1 -C 5 alkyl), OH, N(R 22 ) 2 , CO2R 22 , CON(R 22 ) or -C V F„ where v - 1 to 3 and w = 1 to (2v+l) ; (ii) C 3 -C 8 cycloalkyl; (iii) 15b aryl, optionally substituted with 1-2 substituents independently selected from halogen, phenyl, C 1 -C 5 alkyl, C 1 -C 5 alkoxy, N0 2 , -S (0) 0- 2 (C1-C5 alkyl), OH, N(R 2 ) 2 / C0 R 22 , CON(R 22 ) 2 or -C V F W where v = 1 to 3 and w = 1 to (2v+l) ; C 2 -C 8 alkyl, alkenyl or alkynyl; substituted with 1-2 substituents independentl ' selected from C 1 -C 4 alkyl, C3-C8 cycloalkyl, C 1 -C5 alkoxy, phenoxy, benzyloxy, halogen, NO 2 , CN, CO2R 22 , C0N(R 22 ) 2 , N(R 4 )COR 24 , morpholino, 2-(l- morpholino) ethoxy, N(R 22 ) 2 , N + (R 22 ) 3 , OCOCH3, -CH(R 24 )OR 2 6; -CH(R 24 )OC(=0)R 25 ; -CH(R 24 )OC(=0)OR 26 ; -CH (R 24 ) OC (=0) N (R 25 ) 2 ; -CH (R 24 )N (R 24 ) C (=0) R 24 ; -CH(R 2 )C0 2 R 25 ; -CH(R 4 )CON(R 22 ) 2 ; -CH(R 24 )N(R 22 ) 2 ; 27 15 \ R 22 is selected independently from: H, Ci-Cio alkyl, C3-C10 cycloalkyl, C4-C12 alkylcycloalkyl, aryl, -(C1-C10 alkyl)aryl, or C3-C10 alkoxyalkyl; when two R 22 groups are bonded to a single N, said R 22 groups may alternatively be taken together to form -(CH2)2-5~ or -(CH 2 )0(CH 2 )-; R 24 is selected independently from: H, Ci-Cβ alkyl, C 3 -C 10 cycloalkyl, phenyl, or benzyl; R 25 is selected from: H; IS - Ci-Cβ alkyl or C 3 -C 8 cycloalkyl, said alkyl or cycloalkyl being substituted with 1-2 groups independently selected from: 5 (i) C 1 -C 4 alkyl; (ii) C3-C 8 cycloalkyl; (iii) C 3 .-C 5 alkoxy; (iv) aryl substituted with 0-2 groups independently selected from: 10 halogen, phenyl, Cι~Cξ alkyl, C 1 -C 6 alkoxy, NO 2 , -S (C 1 -C 5 alkyl), -SO(Cι-C 5 alkyl), -S0 2 (C 1 -C 5 alkyl), -OH, -N(R 22 ) 2 , -C0 2 R 22 , -C(=0)N(R 22 ) 2 , or -C V F W where v = 1 15 to 3 and w = 1 to (2v+l); aryl substituted with 0-2 groups independently selected from: halogen, phenyl, Ci-C δ alkyl, Ci-Cβ alkoxy, N0 , -S(Cι-C 5 alkyl), -SO(Cι-C 5 20 alkyl), -SO 2 (C 1 -C5 alkyl), -OH, -N(R 22 ) 2 , -C0 2 R 22 , -C(=0)N(R 22 ) 2 , or -C V F W where v = 1 to 3 and w = 1 to <2v+l); 25 R 26 is selected from: Ci-Cβ alkyl or C 3 -C 8 cycloalkyl, said alkyl or cycloalkyl being substituted with 1-2 groups independently selected from: 30 (i) C 1 -C 4 alkyl; (ii) C 3 -C 8 cycloalkyl; (iii) C 1 -C 5 alkoxy; (iv) aryl substituted with 0-2 groups independently selected from: 35 halogen, phenyl, C 1 -C6 alkyl, Ci-Cβ alkoxy, NO 2 , -S(C 1 -C 5 alkyl), -SO(Cι-C 5 alkyl), -S0 2 (C 1 -C 5 alkyl), -OH, -N(R 22 ) 2 , -CO2R 22 , -C(=0)N(R 22 ) 2 , or -CvFw where v = 1 5 to 3 and w = 1 to (2v+l) ; aryl substituted with 0-2 groups independently selected from: halogen, phenyl, Cι~Ce alkyl, Ci-Cβ alkoxy, N0 2 , -S(Cι-C 5 alkyl), -S0(Cι-C 5 10 alkyl), -SO 2 (C 1 -C 5 alkyl), -OH, -N(R 22 ) 2 , -C0 2 R 22 , -C(=0)N(R 22 ) 2 , or -C V F W where v = 1 to 3 and w = 1 to (2v+l); 15 R 27 is selected from: H Ci-Cβ alkyl or C 3 ~Cβ cycloalkyl, said alkyl or cycloalkyl being substituted with 1-2 groups independently selected 20 from: (i) Ci-Ce alkyl; (ii) C 1 -C 6 alkoxy; (iii) aryl substituted with 0-2 groups independently selected from: 25 halogen, phenyl, Ci-Cβ alkyl, C3.-C 6 alkoxy, NO 2 , -S (C 1 -C5 alkyl), -SO(Cι-C 5 alkyl), -SO 2 (C 1 -C 5 alkyl), -OH, -N(R 22 ) , -C0 2 R 22 , or -C V F„ where v = 1 30 to 3 and w = 1 to (2v+l) ; aryl substituted with 0-2 groups independently selected from: halogen, phenyl, Ci-Cβ alkyl, Ci-Cβ alkoxy, NO 2 , -S(Cι-C 5 alkyl), -SO(Cι-Cs 35 alkyl), -S0 2 (C 1 -C 5 alkyl), -OH, -N(R 22 ) 2 , -.O2R 22 , -C(=0)N(R 22 ) , or -C V F W where v = 1 to 3 and w = 1 to (2v+l); R 28 is selected from: H, C 1 -C 5 alkyl, or benzyl; n is 1 to 4; m is 0 to 3; Y is H or a suitable carboxylate protecting group and can be selected from the group consisting of: alkyl esters such as Ci to C8 alkyl, C5 to Cβ cycloalkylalkyl and t- butyl; aryl esters such as benzyl, substituted benzyl, triphenylmethyl, diphenylmethy1, pentamethylbenzy1,tetramethylbenzy1, and trimethylbenzy1; or esters which can be cleaved by acidolysis, mild base treatment or mild reductive means such as trichloroethyl and phenacyl esters; other protecting groups can be CH2CH2CN, trialkylsilyl, phthalimidomethyl, anthrylmethy1, phenylfluorenyl, 4-picolyl and phenacyl; W is H or an amine protecting group and is selected from the group consisting of: acyl types such as formyl, trifluoroacetyl, phthalyl, and p- toluenesulfonyl; aromatic carbamate types such as benzyloxycarbonyl (Cbz) and substituted benzyloxycarbonyls, 1-(p- biphenyl)-1-methylethoxycarbonyl, and 9- fluorenylmethyloxycarbonyl (Fmoc) ; aliphatic carbamate types such as tert-butyloxycarbonyl (Boc) , ethoxycarbonyl, diisopropylmethoxycarbonyl, and allyloxycarbonyl; cyclic alkyl carbamate types such as cyclopentyloxycarbonyl and 5 adamantyloxycarbony1; alkyl types such as triphenylmethyl and benzyl; trialkylsilane such as trimethylsilane; and thiol containing types such as phenylthiocarbonyl and dithiasuccinoylalkyl-urethane; sulfenyl types 10 such as O-nitrophenylsulfenyl (NPS) and nitropyridylsulfenyl (NPYS) ; and XX is H or a suitable amine protecting group and is selected from the group consisting of: acyl 15 types such as formyl, trifluoroacetyl, phthalyl, and p-toluenesulfonyl; aromatic carbamate types such as benzyloxycarbonyl (Cbz) and substituted benzyloxycarbonyls, 1- (p-biphenyl)-l-methylethoxycarbonyl, and 9- 20 fluorenylmethyloxycarbonyl (Fmoc) ; aliphatic carbamate types such as tert-butyloxycarbonyl (Boc) , ethoxycarbonyl, diisopropylmethoxycarbonyl, and allyloxycarbonyl; cyclic alkyl carbamate 25 types such as cyclopentyloxycarbonyl and adamantyloxycarbonyl; alkyl types such as triphenylmethyl and benzyl; trialkylsilane such as trimethylsilane; and thiol containing types such as phenylthiocarbonyl and 30 dithiasuccinoylalkyl-urethane; sulfenyl types such as O-nitrophenylsulfenyl (NPS) , nitropyridylsulfenyl (NPYS), 2,3, 6-trimethyl- -methoxybenzenesulfonamide (Mtr-NR2)/ 2,4,6- trimethoxybenzenesulfonamide (Mtb-NR2), 2,6- 35 dimethyl-4-methoxybenzenesulfonamide (Mds- NR2), pentamethylbenzenesulfonamide (Pme-NR2) , 2,3,5, 6-tetramethyl-4-methoxybenzene- sulfonamide (Mte-NR2), 4-methoxybenzene- sulfonamide (Mbs-NR2) , 2,4,6- trimethylbenzenesulfonamide (Mts-NR2) , 2,6- dimethoxy-4-methoxybenzenesulfonamide (iMds- NR2) , and 2,2,5,7,8-Pentamethylchroman-6- sulfonamide (Pmc-NR2) . 15. An intermediate compound of claim 14 wherein: W and XX are independently Cbz, t-Boc; .19 is selected from: R 15 and R 18 are independently selected from H, C1-C4 alkyl, phenyl, benzyl, phenyl- (C2-C4) alkyl, C 1 -C 4 alkoxy; R 17 and R 16 are independently H or C 1 -C 4 alkyl; ΪA. R 7 is H, Ci-Ce alkyl, phenyl, halogen, or Cι~ C4 alkoxy; R 11 is H or C1-C3 alkyl; R 12 is H or CH3; R 9 is H, C1-C3 alkyl; R 5 is H, C1-C3 alkyl; R 4 is selected independently at each occurrence from: H; Ci-Cβ alkyl; C2-C8 alkenyl; C2-C8 alkynyl; C3-C8 cycloalkyl; Ci-Cβ alkyl substituted with (i) aryl, optionally substituted with 1-2 substituents independently selected from halogen, phenyl, C1-C5 alkyl, C3.-C5 alkoxy, N0 2 , -S (0) 0-2 (C1-C5 alkyl), OH, N(R 22 ) 2 , CO2R 22 , C0N(R 22 )2 or -C V F W where v = 1 to 3 and w = 1 to (2v+l) ; (ii) C3-C8 cycloalkyl; (iii) aryl, optionally substituted with 1-2 substituents independently selected from halogen, phenyl, C1-C5 alkyl, C1-C5 alkoxy, N0 2 , -S (0) 0-2 (C1-C5 alkyl), OH, N(R 22 )2, C0 2 R 22 , CON(R 22 ) 2 or -C V F W where v = 1 to 3 and w = 1 to (2v+l) ; C2-Cβ alkyl, alkenyl or alkynyl; substituted with 1-2 substituents independently selected from C1-C 4 alkyl, C3-C8 cycloalkyl, C 1 -C5 alkoxy, phenoxy, benzyloxy, halogen, NO2, CN, CO2R 22 , C0N(R )2/ N(R 24 )COR 24 , morpholino, 2-(l- morpholino) ethoxy, N(R 2 ) 2 / N + (R 22 ) 3 , OCOCH3, CF 3 , S ( O ) 0 -2R 22 ; -CH(R 24 )OR 26 ; -CH(R 4 )0C(=0)R 25 ; -CH(R 24 )OC(=0)OR 26 ; -CH(R 24 )OC (=0)N(R 25 )2; -CH(R 24 )C0 R 25 ; m is 2, and n is 3. 16. An intermediate compound of claim 14 wherein: R 2 is C1-C4 alkyl; R 5 , R 9 , R 16 , R 17 and R 18 are H; R 11 , and R 12 , are H or CH3; \ <\ R 15 is H, C1-C4 alkyl, phenyl, benzyl, or phenyl- (C2-C4)alkyl; R 3 is H or C 1 -C 3 alkyl; R4 is selected independently at each occurrence from: H; -CH(R 24 )OC(=0)R 25 ; -CH(R 24 )OC(=0)OR 26 ; -CH 2 OC(=0)N(R 25 y 2 ; -CH 2 CH 2 N(R 22 ) 2 ; -CH(R 24 )C02R 25 ; R 24 is selected independently from: H, Ci-Cβ alkyl, phenyl, or benzyl; R 27 is selected from: C 1 -C 5 alkyl, benzyl or phenyl; m is 2, and n is 3. 17. An intermediate compound of claim 14 wherein: p is 0, p' is 1; R1 9 is phenyl R 5 , R 9 , R 11 , R 12 , and R 14 are H; R 2 is ethyl ; R 3 is methyl; and m is 2, and n is 3; R β is CH2-OBn, CH2~0tBu, CH2~0-tBoc or CH2CO2 ; R 4 is selected independently at each occurrence from: H; -CH(R 2 )OC(=0)R 25 ; -CH(R 2 )OC(=0)OR 26 ; R 24 is C 1 -C 4 linear alkyl or H; R 27 is C 1 -C 4 alkyl, benzyl, or phenyl; and XX is Cbz or Boc.

Inventors: DEGRADO WILLIAM FRANK, DOROW ROBERTA LOUISE, WARD RANDALL KAY, XUE CHU-BIAO, DEGRADO, WILLIAM, FRANK, DOROW, ROBERTA, LOUISE, WARD, RANDALL, KAY, XUE, CHU-BIAO
Applicants: DU PONT MERCK PHARMA, THE DU PONT MERCK PHARMACEUTICAL COMPANY
Application year: 1994
Main classification: C07K7
IPC codes: C07C253, C07C255, C07C271, C07K1, C07K5, C07K7, C07K14